DK2510946T3 - Konjugater af syntetiske tlr-agonister og anvendelser deraf - Google Patents
Konjugater af syntetiske tlr-agonister og anvendelser deraf Download PDFInfo
- Publication number
- DK2510946T3 DK2510946T3 DK12004181.9T DK12004181T DK2510946T3 DK 2510946 T3 DK2510946 T3 DK 2510946T3 DK 12004181 T DK12004181 T DK 12004181T DK 2510946 T3 DK2510946 T3 DK 2510946T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- agonist
- tlr7
- alkyl
- conjugate
- Prior art date
Links
- 239000000556 agonist Substances 0.000 title description 78
- 150000001875 compounds Chemical class 0.000 claims description 125
- 239000000203 mixture Substances 0.000 claims description 62
- 150000002632 lipids Chemical class 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 19
- 208000006673 asthma Diseases 0.000 claims description 18
- 239000002502 liposome Substances 0.000 claims description 15
- 239000002105 nanoparticle Substances 0.000 claims description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 7
- 230000003308 immunostimulating effect Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 235000012000 cholesterol Nutrition 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 229960001438 immunostimulant agent Drugs 0.000 claims 1
- 239000003022 immunostimulating agent Substances 0.000 claims 1
- 102000002689 Toll-like receptor Human genes 0.000 description 96
- 108020000411 Toll-like receptor Proteins 0.000 description 96
- -1 8-substituted amino-9-benzyladenines Chemical class 0.000 description 72
- SHNIBVWXUOEWTA-UHFFFAOYSA-N 4-[[6-amino-2-(2-methoxyethoxy)-8-oxo-7h-purin-9-yl]methyl]benzaldehyde Chemical compound C12=NC(OCCOC)=NC(N)=C2N=C(O)N1CC1=CC=C(C=O)C=C1 SHNIBVWXUOEWTA-UHFFFAOYSA-N 0.000 description 70
- 125000000217 alkyl group Chemical group 0.000 description 63
- 229940044616 toll-like receptor 7 agonist Drugs 0.000 description 62
- 102000004127 Cytokines Human genes 0.000 description 50
- 108090000695 Cytokines Proteins 0.000 description 50
- 241000699670 Mus sp. Species 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 210000004027 cell Anatomy 0.000 description 38
- 125000003118 aryl group Chemical group 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 32
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 32
- 241000193738 Bacillus anthracis Species 0.000 description 31
- 230000000694 effects Effects 0.000 description 31
- 125000000623 heterocyclic group Chemical group 0.000 description 30
- 150000003839 salts Chemical class 0.000 description 30
- 229910052739 hydrogen Inorganic materials 0.000 description 29
- 208000015181 infectious disease Diseases 0.000 description 29
- 239000001257 hydrogen Substances 0.000 description 28
- 229920002521 macromolecule Polymers 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 27
- 238000000034 method Methods 0.000 description 25
- 239000000243 solution Substances 0.000 description 24
- 239000000427 antigen Substances 0.000 description 23
- 108091007433 antigens Proteins 0.000 description 22
- 102000036639 antigens Human genes 0.000 description 22
- 108090000623 proteins and genes Proteins 0.000 description 22
- 229960005486 vaccine Drugs 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 21
- 241000700605 Viruses Species 0.000 description 21
- 150000007523 nucleic acids Chemical class 0.000 description 21
- 125000005647 linker group Chemical group 0.000 description 20
- 108020004707 nucleic acids Proteins 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 206010028980 Neoplasm Diseases 0.000 description 17
- 210000004443 dendritic cell Anatomy 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 241000191967 Staphylococcus aureus Species 0.000 description 16
- 229940065181 bacillus anthracis Drugs 0.000 description 16
- 230000001580 bacterial effect Effects 0.000 description 16
- 150000002431 hydrogen Chemical class 0.000 description 16
- 230000004048 modification Effects 0.000 description 16
- 238000012986 modification Methods 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 241000124008 Mammalia Species 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 125000003545 alkoxy group Chemical group 0.000 description 15
- 230000021615 conjugation Effects 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 230000003389 potentiating effect Effects 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 15
- 230000009885 systemic effect Effects 0.000 description 15
- 239000002671 adjuvant Substances 0.000 description 14
- 210000004979 bone marrow derived macrophage Anatomy 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 230000028993 immune response Effects 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 125000001072 heteroaryl group Chemical group 0.000 description 13
- 230000004044 response Effects 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- 125000004404 heteroalkyl group Chemical group 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 241000192125 Firmicutes Species 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 11
- 150000001413 amino acids Chemical class 0.000 description 11
- 125000004093 cyano group Chemical group *C#N 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 210000001163 endosome Anatomy 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- 238000012384 transportation and delivery Methods 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 10
- 229910003827 NRaRb Inorganic materials 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 125000003277 amino group Chemical group 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 230000016396 cytokine production Effects 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 231100000252 nontoxic Toxicity 0.000 description 10
- 230000003000 nontoxic effect Effects 0.000 description 10
- 229910052717 sulfur Inorganic materials 0.000 description 10
- 208000035143 Bacterial infection Diseases 0.000 description 9
- 108010065805 Interleukin-12 Proteins 0.000 description 9
- 102000013462 Interleukin-12 Human genes 0.000 description 9
- 150000001720 carbohydrates Chemical class 0.000 description 9
- 235000014633 carbohydrates Nutrition 0.000 description 9
- 239000000412 dendrimer Substances 0.000 description 9
- 229920000736 dendritic polymer Polymers 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 150000002367 halogens Chemical class 0.000 description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 230000009385 viral infection Effects 0.000 description 9
- 241000894006 Bacteria Species 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 108010050904 Interferons Proteins 0.000 description 8
- 102000014150 Interferons Human genes 0.000 description 8
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 241000712461 unidentified influenza virus Species 0.000 description 8
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 7
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 7
- 208000036142 Viral infection Diseases 0.000 description 7
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 230000002163 immunogen Effects 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 230000001681 protective effect Effects 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 241001493065 dsRNA viruses Species 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 230000000813 microbial effect Effects 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000013296 A/J mouse Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 241000700721 Hepatitis B virus Species 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 239000012190 activator Substances 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 150000004665 fatty acids Chemical group 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 229940047124 interferons Drugs 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 244000052769 pathogen Species 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 5
- 210000002345 respiratory system Anatomy 0.000 description 5
- 230000004043 responsiveness Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000012265 solid product Substances 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 125000000547 substituted alkyl group Chemical group 0.000 description 5
- 125000003107 substituted aryl group Chemical group 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- 102000009016 Cholera Toxin Human genes 0.000 description 4
- 108010049048 Cholera Toxin Proteins 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 4
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 4
- 108010002352 Interleukin-1 Proteins 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 241000272168 Laridae Species 0.000 description 4
- 108010058846 Ovalbumin Proteins 0.000 description 4
- 241000725643 Respiratory syncytial virus Species 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 206010041925 Staphylococcal infections Diseases 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 4
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 4
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 4
- 102100040247 Tumor necrosis factor Human genes 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 229960002751 imiquimod Drugs 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000002458 infectious effect Effects 0.000 description 4
- 231100000518 lethal Toxicity 0.000 description 4
- 230000001665 lethal effect Effects 0.000 description 4
- 230000035800 maturation Effects 0.000 description 4
- 229940092253 ovalbumin Drugs 0.000 description 4
- 150000003904 phospholipids Chemical class 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 150000004804 polysaccharides Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 3
- BAXBGOILCIVNDA-UHFFFAOYSA-N 4-[[6-amino-8-methoxy-2-(2-methoxyethoxy)purin-9-yl]methyl]benzonitrile Chemical compound C12=NC(OCCOC)=NC(N)=C2N=C(OC)N1CC1=CC=C(C#N)C=C1 BAXBGOILCIVNDA-UHFFFAOYSA-N 0.000 description 3
- 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 description 3
- 108010077805 Bacterial Proteins Proteins 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 108010014726 Interferon Type I Proteins 0.000 description 3
- 102000002227 Interferon Type I Human genes 0.000 description 3
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 3
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000607142 Salmonella Species 0.000 description 3
- 241000191940 Staphylococcus Species 0.000 description 3
- 229940124614 TLR 8 agonist Drugs 0.000 description 3
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000013566 allergen Substances 0.000 description 3
- 201000009961 allergic asthma Diseases 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 125000003435 aroyl group Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000002051 biphasic effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 229960003405 ciprofloxacin Drugs 0.000 description 3
- 230000001010 compromised effect Effects 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000001024 immunotherapeutic effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 229960003299 ketamine Drugs 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 206010025135 lupus erythematosus Diseases 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 238000013160 medical therapy Methods 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 210000005087 mononuclear cell Anatomy 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229950010550 resiquimod Drugs 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 2
- VZSVJCPULAOEOJ-UHFFFAOYSA-N 4-[[6-amino-8-methoxy-2-(2-methoxyethoxy)purin-9-yl]methyl]benzoic acid Chemical compound C12=NC(OCCOC)=NC(N)=C2N=C(OC)N1CC1=CC=C(C(O)=O)C=C1 VZSVJCPULAOEOJ-UHFFFAOYSA-N 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- YYCDGEZXHXHLGW-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2-methoxyethoxy)-7h-purin-8-one Chemical class C12=NC(OCCOC)=NC(N)=C2NC(=O)N1CC1=CC=CC=C1 YYCDGEZXHXHLGW-UHFFFAOYSA-N 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- 101000609762 Gallus gallus Ovalbumin Proteins 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000186779 Listeria monocytogenes Species 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 101000930477 Mus musculus Albumin Proteins 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108010089430 Phosphoproteins Proteins 0.000 description 2
- 102000007982 Phosphoproteins Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 206010062106 Respiratory tract infection viral Diseases 0.000 description 2
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 229940124613 TLR 7/8 agonist Drugs 0.000 description 2
- 108700012920 TNF Proteins 0.000 description 2
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 208000009621 actinic keratosis Diseases 0.000 description 2
- 230000004721 adaptive immunity Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 208000022338 anthrax infection Diseases 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000003190 augmentative effect Effects 0.000 description 2
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 208000020082 intraepithelial neoplasia Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000001325 log-rank test Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- 244000000010 microbial pathogen Species 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000004713 phosphodiesters Chemical group 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920000962 poly(amidoamine) Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000012460 protein solution Substances 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 229910052705 radium Inorganic materials 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229910052701 rubidium Inorganic materials 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 208000014794 superficial urinary bladder carcinoma Diseases 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
- LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 1
- LVNGJLRDBYCPGB-UHFFFAOYSA-N 1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FBFJOZZTIXSPPR-UHFFFAOYSA-N 1-(4-aminobutyl)-2-(ethoxymethyl)imidazo[4,5-c]quinolin-4-amine Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CCCCN)C3=C(N)N=C21 FBFJOZZTIXSPPR-UHFFFAOYSA-N 0.000 description 1
- VQFKFAKEUMHBLV-BYSUZVQFSA-N 1-O-(alpha-D-galactosyl)-N-hexacosanoylphytosphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)[C@H](O)CCCCCCCCCCCCCC)CO[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQFKFAKEUMHBLV-BYSUZVQFSA-N 0.000 description 1
- HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 description 1
- LDKSCZJUIURGMW-UHFFFAOYSA-N 1-isothiocyanato-3-methylsulfanylpropane Chemical group CSCCCN=C=S LDKSCZJUIURGMW-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- TXHAHOVNFDVCCC-UHFFFAOYSA-N 2-(tert-butylazaniumyl)acetate Chemical compound CC(C)(C)NCC(O)=O TXHAHOVNFDVCCC-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- RGNOTKMIMZMNRX-XVFCMESISA-N 2-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-4-one Chemical compound NC1=NC(=O)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RGNOTKMIMZMNRX-XVFCMESISA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- VDCRFBBZFHHYGT-IOSLPCCCSA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-enyl-3h-purine-6,8-dione Chemical compound O=C1N(CC=C)C=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VDCRFBBZFHHYGT-IOSLPCCCSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- HCGYMSSYSAKGPK-UHFFFAOYSA-N 2-nitro-1h-indole Chemical compound C1=CC=C2NC([N+](=O)[O-])=CC2=C1 HCGYMSSYSAKGPK-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- BXRLWGXPSRYJDZ-UHFFFAOYSA-N 3-cyanoalanine Chemical compound OC(=O)C(N)CC#N BXRLWGXPSRYJDZ-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 description 1
- APCLRHPWFCQIMG-UHFFFAOYSA-N 4-(5,6-dimethoxy-1-benzothiophen-2-yl)-4-oxobutanoic acid Chemical compound C1=C(OC)C(OC)=CC2=C1SC(C(=O)CCC(O)=O)=C2 APCLRHPWFCQIMG-UHFFFAOYSA-N 0.000 description 1
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 1
- VZOAGHRMLRLXBE-UHFFFAOYSA-N 4-[(2,6-dichloropurin-9-yl)methyl]benzonitrile Chemical compound C12=NC(Cl)=NC(Cl)=C2N=CN1CC1=CC=C(C#N)C=C1 VZOAGHRMLRLXBE-UHFFFAOYSA-N 0.000 description 1
- LDMVWEVNROLMHZ-UHFFFAOYSA-N 4-[[6-amino-8-bromo-2-(2-methoxyethoxy)purin-9-yl]methyl]benzonitrile Chemical compound C12=NC(OCCOC)=NC(N)=C2N=C(Br)N1CC1=CC=C(C#N)C=C1 LDMVWEVNROLMHZ-UHFFFAOYSA-N 0.000 description 1
- RUBGVJBUQLBBCN-UHFFFAOYSA-N 4-[[6-amino-8-methoxy-2-(2-methoxyethoxy)purin-9-yl]methyl]benzaldehyde Chemical compound C12=NC(OCCOC)=NC(N)=C2N=C(OC)N1CC1=CC=C(C=O)C=C1 RUBGVJBUQLBBCN-UHFFFAOYSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical class BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical class IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CIUUIPMOFZIWIZ-UHFFFAOYSA-N Bropirimine Chemical compound NC1=NC(O)=C(Br)C(C=2C=CC=CC=2)=N1 CIUUIPMOFZIWIZ-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010008263 Cervical dysplasia Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010008531 Chills Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- DFCAFRGABIXSDS-UHFFFAOYSA-N Cycloate Chemical compound CCSC(=O)N(CC)C1CCCCC1 DFCAFRGABIXSDS-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010069304 Exfoliatins Proteins 0.000 description 1
- 208000001382 Experimental Melanoma Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 108010040721 Flagellin Proteins 0.000 description 1
- 241000589602 Francisella tularensis Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010069767 H1N1 influenza Diseases 0.000 description 1
- 241000711557 Hepacivirus Species 0.000 description 1
- 101000595548 Homo sapiens TIR domain-containing adapter molecule 1 Proteins 0.000 description 1
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- DGYHPLMPMRKMPD-UHFFFAOYSA-N L-propargyl glycine Natural products OC(=O)C(N)CC#C DGYHPLMPMRKMPD-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 101150092365 MSA2 gene Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- LMSMREVZQWXONY-UHFFFAOYSA-N N-(2,5-dioxopyrrolidin-1-yl)-6-hydrazinylpyridine-3-carboxamide propan-2-ylidenehydrazine Chemical compound CC(C)=NN.C1=NC(NN)=CC=C1C(=O)NN1C(=O)CCC1=O LMSMREVZQWXONY-UHFFFAOYSA-N 0.000 description 1
- 229920002505 N-(Carbonyl-Methoxypolyethylene Glycol 2000)-1,2-Distearoyl-Sn-Glycero-3-Phosphoethanolamine Polymers 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010035742 Pneumonitis Diseases 0.000 description 1
- 208000037062 Polyps Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 101100240989 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nrd1 gene Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 206010041235 Snoring Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102100036073 TIR domain-containing adapter molecule 1 Human genes 0.000 description 1
- 229940124615 TLR 7 agonist Drugs 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 229940123384 Toll-like receptor (TLR) agonist Drugs 0.000 description 1
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 101710179195 Uncharacterized protein IRL6 Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 239000000809 air pollutant Substances 0.000 description 1
- 231100001243 air pollutant Toxicity 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229950009494 bropirimine Drugs 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001669 calcium Chemical class 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000005323 carbonate salts Chemical class 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000000453 cell autonomous effect Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000005860 defense response to virus Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical group CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 125000003916 ethylene diamine group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229940118764 francisella tularensis Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005908 glyceryl ester group Chemical group 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 208000027136 gram-positive bacterial infections Diseases 0.000 description 1
- 210000005255 gram-positive cell Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 201000007119 infective endocarditis Diseases 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 208000037797 influenza A Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000019734 interleukin-12 production Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229950005634 loxoribine Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- 108010051618 macrophage stimulatory lipopeptide 2 Proteins 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
- 229960002329 methacholine Drugs 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229950000844 mizoribine Drugs 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 1
- CQYBNXGHMBNGCG-RNJXMRFFSA-N octahydroindole-2-carboxylic acid Chemical compound C1CCC[C@H]2N[C@H](C(=O)O)C[C@@H]21 CQYBNXGHMBNGCG-RNJXMRFFSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 102000007863 pattern recognition receptors Human genes 0.000 description 1
- 108010089193 pattern recognition receptors Proteins 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- USRGIUJOYOXOQJ-GBXIJSLDSA-N phosphothreonine Chemical compound OP(=O)(O)O[C@H](C)[C@H](N)C(O)=O USRGIUJOYOXOQJ-GBXIJSLDSA-N 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 210000004879 pulmonary tissue Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 208000020352 skin basal cell carcinoma Diseases 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 230000027849 smooth muscle hyperplasia Effects 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- SRLOHQKOADWDBV-NRONOFSHSA-M sodium;[(2r)-2,3-di(octadecanoyloxy)propyl] 2-(2-methoxyethoxycarbonylamino)ethyl phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCCNC(=O)OCCOC)OC(=O)CCCCCCCCCCCCCCCCC SRLOHQKOADWDBV-NRONOFSHSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- DFVFTMTWCUHJBL-BQBZGAKWSA-N statine Chemical compound CC(C)C[C@H](N)[C@@H](O)CC(O)=O DFVFTMTWCUHJBL-BQBZGAKWSA-N 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004960 subcellular localization Effects 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 201000010740 swine influenza Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 230000024664 tolerance induction Effects 0.000 description 1
- 239000003970 toll like receptor agonist Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 1
- 229950004616 tribromoethanol Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/07—Bacillus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/085—Staphylococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biotechnology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Claims (5)
1. Forbindelse ifølge den følgende formel
2. Farmaceutisk sammensætning omfattende forbindelsen ifølge krav 1.
3. Sammensætning ifølge krav 2, som omfatter liposomnanopartikler omfattende forbindelsen ifølge krav 1 med kolesterol, DOPE og andre lipider, der har en hydrodynamisk diameter på omkring 100 nm.
4. Forbindelse ifølge krav 1 til anvendelse som et immunostimulerende middel.
5. Forbindelse ifølge krav 1 til anvendelse i forebyggelse, behandling eller inhibition af astma.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US88869907P | 2007-02-07 | 2007-02-07 | |
| EP08799591.6A EP2125007B9 (en) | 2007-02-07 | 2008-02-07 | Conjugates of synthetic tlr agonists and uses therefor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2510946T3 true DK2510946T3 (da) | 2015-11-02 |
Family
ID=39766655
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK12004181.9T DK2510946T3 (da) | 2007-02-07 | 2008-02-07 | Konjugater af syntetiske tlr-agonister og anvendelser deraf |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US8357374B2 (da) |
| EP (2) | EP2125007B9 (da) |
| JP (2) | JP5425642B2 (da) |
| KR (1) | KR20090109121A (da) |
| CN (1) | CN101790380B (da) |
| AU (1) | AU2008227128B2 (da) |
| CA (1) | CA2677733A1 (da) |
| DK (1) | DK2510946T3 (da) |
| EA (1) | EA019151B1 (da) |
| ES (2) | ES2552471T3 (da) |
| HU (1) | HUE025555T2 (da) |
| IL (1) | IL200240A (da) |
| PL (2) | PL2510946T3 (da) |
| PT (1) | PT2510946E (da) |
| SI (1) | SI2510946T1 (da) |
| WO (1) | WO2008115319A2 (da) |
| ZA (1) | ZA200906094B (da) |
Families Citing this family (122)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2577514T3 (es) * | 2005-08-22 | 2016-07-15 | The Regents Of The University Of California | Antagonistas de TLR |
| EP2029597A4 (en) | 2006-05-31 | 2011-11-23 | Univ California | purine analogs |
| ES2552471T3 (es) | 2007-02-07 | 2015-11-30 | The Regents Of The University Of California | Conjugados de agonistas de TLR sintéticos y usos de los mismos |
| WO2009049365A1 (en) * | 2007-10-15 | 2009-04-23 | Cooperative Research Centre For Asthma | A method of prophylaxis and agents for use therein |
| EA201001264A1 (ru) * | 2008-02-07 | 2011-04-29 | Дзе Регентс Оф Дзе Юниверсити Оф Калифорния | Способ лечения заболеваний мочевого пузыря с помощью активатора tlr7 |
| WO2010088924A1 (en) | 2009-02-06 | 2010-08-12 | Telormedix Sa | Pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration |
| KR20110117705A (ko) | 2009-02-11 | 2011-10-27 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 톨-유사 수용체 조정제 및 질병의 치료 |
| CA2762653A1 (en) * | 2009-05-27 | 2010-12-02 | Selecta Biosciences, Inc. | Immunomodulatory agent-polymeric compounds |
| US8962652B2 (en) | 2009-10-22 | 2015-02-24 | Gilead Sciences, Inc. | Derivatives of purine or deazapurine useful for the treatment of (inter alia) viral infections |
| US20130202629A1 (en) * | 2010-04-30 | 2013-08-08 | The Regents Of The University Of California | Uses of phospholipid conjugates of synthetic tlr7 agonists |
| US9050319B2 (en) | 2010-04-30 | 2015-06-09 | Telormedix, Sa | Phospholipid drug analogs |
| NZ603155A (en) * | 2010-04-30 | 2014-06-27 | Telormedix Sa | Phospholipid drug analogs |
| WO2011134669A1 (en) * | 2010-04-30 | 2011-11-03 | Telormedix Sa | Methods for inducing an immune response |
| AU2011258165B2 (en) | 2010-05-26 | 2016-11-17 | Selecta Biosciences, Inc. | Dose selection of adjuvanted synthetic nanocarriers |
| US20120083473A1 (en) | 2010-09-21 | 2012-04-05 | Johanna Holldack | Treatment of conditions by toll-like receptor modulators |
| US20140031250A1 (en) | 2010-10-07 | 2014-01-30 | David Tsai Ting | Biomarkers of Cancer |
| WO2012061717A1 (en) | 2010-11-05 | 2012-05-10 | Selecta Biosciences, Inc. | Modified nicotinic compounds and related methods |
| HUE055286T2 (hu) | 2011-04-08 | 2021-11-29 | Janssen Sciences Ireland Unlimited Co | Pirimidinszármazékok vírusfertõzések kezelésére |
| EP3153180A1 (en) * | 2011-06-03 | 2017-04-12 | 3M Innovative Properties Company | Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom |
| WO2012167088A1 (en) | 2011-06-03 | 2012-12-06 | 3M Innovative Properties Company | Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom |
| JP2014521687A (ja) | 2011-07-29 | 2014-08-28 | セレクタ バイオサイエンシーズ インコーポレーテッド | 体液性および細胞傷害性tリンパ球(ctl)免疫応答を生成する合成ナノキャリア |
| RS57851B1 (sr) | 2011-11-09 | 2018-12-31 | Janssen Sciences Ireland Uc | Purinski derivati za tretman viralnih infekcija |
| JP6375289B2 (ja) | 2012-04-05 | 2018-08-15 | マサチューセッツ インスティテュート オブ テクノロジー | 免疫刺激組成物およびその使用方法 |
| CA2874800C (en) | 2012-07-13 | 2021-04-06 | Janssen R&D Ireland | Macrocyclic purines for the treatment of viral infections |
| CN112587671A (zh) | 2012-07-18 | 2021-04-02 | 博笛生物科技有限公司 | 癌症的靶向免疫治疗 |
| WO2014052828A1 (en) | 2012-09-27 | 2014-04-03 | The Regents Of The University Of California | Compositions and methods for modulating tlr4 |
| CN102993265B (zh) * | 2012-10-10 | 2015-05-13 | 深圳大学 | 免疫受体调节剂偶联体及其制备方法和应用、制备其的偶联前体以及合成偶联前体的化合物 |
| LT2906563T (lt) | 2012-10-10 | 2018-06-11 | Janssen Sciences Ireland Uc | Pirolo[3,2-d]pirimidino dariniai virusinių infekcijų ir kitų ligų gydymui |
| EP2925729B1 (en) | 2012-11-16 | 2017-10-18 | Janssen Sciences Ireland UC | Heterocyclic substituted 2-amino-quinazoline derivatives for the treatment of viral infections |
| WO2014128189A1 (en) | 2013-02-21 | 2014-08-28 | Janssen R&D Ireland | 2-aminopyrimidine derivatives for the treatment of viral infections |
| EP2958889B1 (en) * | 2013-02-25 | 2017-03-22 | The Scripps Research Institute | Neoseptins: small molecule adjuvants |
| EP2968501A4 (en) * | 2013-03-14 | 2017-02-15 | Rongfu Wang | Methods and compositions for modulating regulatory t cell function |
| WO2014144365A1 (en) * | 2013-03-15 | 2014-09-18 | University Of Maryland, College Park | Nano-liposomal formulations and methods of use |
| AU2014242954B2 (en) | 2013-03-29 | 2018-03-15 | Janssen Sciences Ireland Uc | Macrocyclic deaza-purinones for the treatment of viral infections |
| SG11201509520QA (en) | 2013-05-24 | 2015-12-30 | Janssen Sciences Ireland Uc | Pyridone derivatives for the treatment of viral infections and further diseases |
| BR112015032546B1 (pt) | 2013-06-27 | 2022-05-17 | Janssen Sciences Ireland Uc | Derivados de pirrolo[3,2-d]pirimidina e composição farmacêutica que os compreende para o tratamento de infecções virais e outras doenças |
| KR102322425B1 (ko) | 2013-07-30 | 2021-11-05 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 바이러스 감염의 치료를 위한 티에노[3,2-d]피리미딘 유도체 |
| EP3033089A2 (en) * | 2013-08-16 | 2016-06-22 | The Regents of The University of California | Uses of phospholipid conjugates of synthetic tlr7 agonists |
| GB201321242D0 (en) | 2013-12-02 | 2014-01-15 | Immune Targeting Systems Its Ltd | Immunogenic compound |
| GB201321737D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| CN105899539B (zh) | 2014-01-10 | 2021-11-09 | 博笛生物科技有限公司 | 用于免疫疗法的化合物和组合物 |
| US10301624B2 (en) | 2014-06-25 | 2019-05-28 | The General Hospital Corporation | Targeting human satellite II (HSATII) |
| EP3166976B2 (en) | 2014-07-09 | 2026-04-08 | Birdie Biopharmaceuticals Inc. | Anti-pd-l1 combinations for treating tumors |
| US9918959B2 (en) | 2014-08-06 | 2018-03-20 | The Board Of Regents Of The University Of Texas System | TLR-independent small molecule adjuvants |
| HUE054672T2 (hu) * | 2014-08-15 | 2021-09-28 | Chia Tai Tianqing Pharmaceutical Group Co Ltd | TLR7 agonistaként alkalmazott pirrolopirimidin vegyületek |
| CN112587672A (zh) | 2014-09-01 | 2021-04-02 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-pd-l1结合物 |
| CA2973878A1 (en) | 2015-01-22 | 2016-07-28 | University Of Massachusetts | Cancer immunotherapy |
| MX375989B (es) * | 2015-05-26 | 2025-03-07 | Ohio State Innovation Foundation | Estrategia de vacuna basada en nanoparticulas contra el virus de la influenza porcina. |
| CA2990852A1 (en) | 2015-06-26 | 2016-12-29 | Beth Israel Deaconess Medical Center, Inc. | Cancer therapy targeting tetraspanin 33 (tspan33) in myeloid derived suppressor cells |
| ES2805724T3 (es) * | 2015-09-29 | 2021-02-15 | Sumitomo Dainippon Pharma Co Ltd | Compuestos de adenina conjugados y su uso como adyuvantes de vacunas |
| CN105311032B (zh) * | 2015-11-09 | 2018-09-25 | 深圳大学 | Tlr7激动剂与酪氨酸激酶抑制剂联用在制备抗肿瘤药物中的应用 |
| CN105315281B (zh) * | 2015-11-16 | 2017-04-19 | 深圳大学 | 化合物i和化合物ii及其制备方法和应用 |
| CN115350279A (zh) | 2016-01-07 | 2022-11-18 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-her2组合 |
| CN115252792A (zh) | 2016-01-07 | 2022-11-01 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-egfr组合 |
| CN106943596A (zh) | 2016-01-07 | 2017-07-14 | 博笛生物科技(北京)有限公司 | 用于治疗肿瘤的抗-cd20组合 |
| US11266602B2 (en) | 2016-05-16 | 2022-03-08 | Infectious Disease Research Institute | PEGylated liposomes and methods of use |
| US11697851B2 (en) | 2016-05-24 | 2023-07-11 | The Regents Of The University Of California | Early ovarian cancer detection diagnostic test based on mRNA isoforms |
| AU2017289418B2 (en) | 2016-07-01 | 2021-06-03 | Janssen Sciences Ireland Unlimited Company | Dihydropyranopyrimidines for the treatment of viral infections |
| WO2018013924A1 (en) | 2016-07-15 | 2018-01-18 | Massachusetts Institute Of Technology | Synthetic nanoparticles for delivery of immunomodulatory compounds |
| JP7274415B2 (ja) | 2016-09-29 | 2023-05-16 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | ウイルス感染症および他の疾患を処置するためのピリミジンプロドラッグ |
| WO2018077385A1 (en) * | 2016-10-25 | 2018-05-03 | Biontech Rna Pharmaceuticals Gmbh | Dose determination for immunotherapeutic agents |
| CA3037046A1 (en) | 2016-10-31 | 2018-05-03 | University Of Massachusetts | Targeting microrna-101-3p in cancer therapy |
| US11471515B2 (en) | 2016-11-09 | 2022-10-18 | The Brigham And Women's Hospital, Inc. | Restoration of tumor suppression using MRNA-based delivery system |
| US10610104B2 (en) | 2016-12-07 | 2020-04-07 | Progenity, Inc. | Gastrointestinal tract detection methods, devices and systems |
| CA3046019A1 (en) | 2016-12-14 | 2018-06-21 | Progenity Inc. | Treatment of a disease of the gastrointestinal tract with a tlr modulator |
| US11986480B2 (en) | 2017-02-03 | 2024-05-21 | Tohoku University | Heterocyclic compound |
| CN118515666A (zh) | 2017-04-27 | 2024-08-20 | 博笛生物科技有限公司 | 2-氨基-喹啉衍生物 |
| IL312120B2 (en) | 2017-06-23 | 2025-06-01 | Birdie Biopharmaceuticals Inc | Pharmaceutical compositions |
| WO2019012107A1 (en) | 2017-07-13 | 2019-01-17 | Danmarks Tekniske Universitet | CATIONIC LIPOSOMES |
| US10494370B2 (en) | 2017-08-16 | 2019-12-03 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor |
| US10472361B2 (en) | 2017-08-16 | 2019-11-12 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a benzotriazole moiety, conjugates thereof, and methods and uses therefor |
| US10457681B2 (en) | 2017-08-16 | 2019-10-29 | Bristol_Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor |
| US10487084B2 (en) | 2017-08-16 | 2019-11-26 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a heterobiaryl moiety, conjugates thereof, and methods and uses therefor |
| US10508115B2 (en) | 2017-08-16 | 2019-12-17 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor |
| US11814623B2 (en) | 2018-01-30 | 2023-11-14 | University Of Massachusetts | Methods of treating a wound using epigenetic regulation |
| JP2021512956A (ja) | 2018-02-06 | 2021-05-20 | ザ ジェネラル ホスピタル コーポレイション | 腫瘍免疫応答のバイオマーカーとしてのリピートrna |
| TW202415645A (zh) | 2018-03-01 | 2024-04-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | 2,4-二胺基喹唑啉衍生物及其醫學用途 |
| CN110317202B (zh) * | 2018-03-30 | 2021-12-24 | 江苏恒瑞医药股份有限公司 | 氰基吡咯并杂芳基类衍生物、其制备方法及其在医药上的应用 |
| CN108379591B (zh) | 2018-04-03 | 2022-03-29 | 深圳大学 | 免疫激动剂靶向化合物的合成及其应用 |
| WO2019196918A1 (zh) * | 2018-04-13 | 2019-10-17 | 罗欣药业(上海)有限公司 | 五元杂环并嘧啶类化合物、药物组合物及用途 |
| US20210371440A1 (en) * | 2018-04-13 | 2021-12-02 | Glaxosmithkline Biologicals Sa | Tlr7 and / or tlr8 agonists |
| WO2019209811A1 (en) | 2018-04-24 | 2019-10-31 | Bristol-Myers Squibb Company | Macrocyclic toll-like receptor 7 (tlr7) agonists |
| US11554120B2 (en) | 2018-08-03 | 2023-01-17 | Bristol-Myers Squibb Company | 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor |
| EP3841112A1 (en) | 2018-08-24 | 2021-06-30 | Codiak BioSciences, Inc. | Extracellular vesicles targeting dendritic cells and uses thereof |
| US10765633B2 (en) * | 2018-12-17 | 2020-09-08 | Eisai R&D Management Co., Ltd | Formulation comprising liposomes |
| MX2021009337A (es) | 2019-02-04 | 2021-10-13 | Codiak Biosciences Inc | Cadenas principales de proteínas de la membrana para la modificación genética de exosomas. |
| CA3132994A1 (en) * | 2019-03-14 | 2020-09-17 | The Regents Of The University Of California | Tlr4 and tlr7 ligand formulations as vaccine adjuvants |
| EP3941511A2 (en) | 2019-03-20 | 2022-01-26 | Massachusetts Institute of Technology | Uses of amphiphiles in immune cell therapy and compositions therefor |
| WO2020191369A1 (en) | 2019-03-21 | 2020-09-24 | Codiak Biosciences, Inc. | Process for preparing extracellular vesicles |
| CN114080232A (zh) | 2019-03-21 | 2022-02-22 | 科迪亚克生物科学公司 | 用于疫苗递送的细胞外囊泡 |
| KR20210141554A (ko) | 2019-03-21 | 2021-11-23 | 코디악 바이오사이언시즈, 인크. | 세포외 소포 접합체 및 이의 용도 |
| US20220251200A1 (en) | 2019-07-03 | 2022-08-11 | Codiak Biosciences, Inc. | Extracellular vesicles targeting t cells and uses thereof |
| MX2022003398A (es) | 2019-09-19 | 2022-04-19 | Univ Danmarks Tekniske | Composicion micelar inmunoestimulante. |
| CA3152478A1 (en) | 2019-09-25 | 2021-04-01 | Codiak Biosciences, Inc. | Extracellular vesicle compositions |
| WO2021126281A1 (en) | 2019-12-20 | 2021-06-24 | Nammi Therapeutics, Inc. | Formulated and/or co-formulated liposome compositions containing toll-like receptor ("tlr") agonist prodrugs useful in the treatment of cancer and methods thereof |
| US20230348468A1 (en) | 2020-01-27 | 2023-11-02 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| KR20220132601A (ko) | 2020-01-27 | 2022-09-30 | 브리스톨-마이어스 스큅 컴퍼니 | 톨-유사 수용체 7 (TLR7) 효능제로서의 1H-피라졸로[4,3-d]피리미딘 화합물 |
| US20230144824A1 (en) | 2020-01-27 | 2023-05-11 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| KR20220132589A (ko) | 2020-01-27 | 2022-09-30 | 브리스톨-마이어스 스큅 컴퍼니 | 톨-유사 수용체 7 (TLR7) 효능제로서의 1H-피라졸로[4,3-d]피리미딘 화합물 |
| US20230131192A1 (en) | 2020-01-27 | 2023-04-27 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| CN115151546A (zh) | 2020-01-27 | 2022-10-04 | 百时美施贵宝公司 | 作为Toll样受体7(TLR7)激动剂的C3-取代的1H-吡唑并[4,3-d]嘧啶化合物 |
| JP2023512204A (ja) | 2020-01-27 | 2023-03-24 | ブリストル-マイヤーズ スクイブ カンパニー | トール様受容体7(TLR7)アゴニストとしての1H-ピラゾロ[4,3-d]ピリミジン化合物 |
| US12485123B2 (en) | 2020-01-27 | 2025-12-02 | Bristol-Myers Squibb Company | 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists |
| WO2021154663A1 (en) | 2020-01-27 | 2021-08-05 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| JP7735291B2 (ja) | 2020-02-21 | 2025-09-08 | エーアールエス ファーマシューティカルズ、インコーポレイテッド | ネクチン-4抗体コンジュゲートおよびその使用 |
| US20230107927A1 (en) | 2020-02-28 | 2023-04-06 | First Wave Bio, Inc. | Methods of treating iatrogenic autoimmune colitis |
| WO2021184017A1 (en) | 2020-03-13 | 2021-09-16 | Codiak Biosciences, Inc. | Extracellular vesicles for treating neurological disorders |
| JP2023518414A (ja) | 2020-03-20 | 2023-05-01 | コディアック バイオサイエンシーズ, インコーポレイテッド | 治療のための細胞外小胞 |
| EP4149550A4 (en) * | 2020-05-15 | 2024-07-03 | The Board of Trustees of the Leland Stanford Junior University | TOLL-LIKE RECEPTOR (TLR) AGONIST NANOPARTICLES AND USES THEREOF |
| WO2021237100A1 (en) | 2020-05-21 | 2021-11-25 | Codiak Biosciences, Inc. | Methods of targeting extracellular vesicles to lung |
| WO2021248133A1 (en) | 2020-06-05 | 2021-12-09 | Codiak Biosciences, Inc. | Anti-transferrin extracellular vesicles |
| CN111892648B (zh) * | 2020-06-08 | 2022-08-26 | 中国科学院上海药物研究所 | 偶联tlr7激动剂的新型冠状病毒多肽疫苗及其应用 |
| JP2023532304A (ja) | 2020-07-01 | 2023-07-27 | エーアールエス ファーマシューティカルズ オペレーションズ,インク. | 抗asgr1抗体コンジュゲートおよびその使用 |
| AU2021300632A1 (en) | 2020-07-02 | 2023-02-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Method of achieving HIV viral remission using long-acting antiretroviral agents |
| US20240241020A1 (en) | 2020-09-23 | 2024-07-18 | Lonza Sales Ag | Process for preparing extracellular vesicles |
| WO2022066898A2 (en) | 2020-09-23 | 2022-03-31 | Codiak Biosciences, Inc. | Methods of producing extracellular vesicles |
| WO2022066883A1 (en) | 2020-09-23 | 2022-03-31 | Codiak Biosciences, Inc. | Extracellular vesicles comprising kras antigens and uses thereof |
| CA3196221A1 (en) * | 2020-10-21 | 2022-04-28 | Univerza V Ljubljani | Conjugated tlr7 and nod2 agonists |
| US20240197759A1 (en) | 2021-03-25 | 2024-06-20 | Danmarks Tekniske Universitet | Immune stimulating nanoparticle composition |
| CN114391102B (zh) * | 2021-05-27 | 2025-02-14 | 中科蓝华(广州)生物医药技术有限公司 | 一种分析cd303+树突状细胞亚群表型和功能的方法及试剂盒 |
| CN118574618A (zh) * | 2021-11-03 | 2024-08-30 | 艾德森特克斯治疗股份有限公司 | 药物偶联物及其制备与使用方法 |
| CN116162088B (zh) * | 2022-12-14 | 2025-03-11 | 江苏省农业科学院 | 一种Toll样受体7激动剂纳米颗粒及其制备方法与应用 |
Family Cites Families (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4559157A (en) | 1983-04-21 | 1985-12-17 | Creative Products Resource Associates, Ltd. | Cosmetic applicator useful for skin moisturizing |
| LU84979A1 (fr) | 1983-08-30 | 1985-04-24 | Oreal | Composition cosmetique ou pharmaceutique sous forme aqueuse ou anhydre dont la phase grasse contient un polyether oligomere et polyethers oligomeres nouveaux |
| IL73534A (en) | 1983-11-18 | 1990-12-23 | Riker Laboratories Inc | 1h-imidazo(4,5-c)quinoline-4-amines,their preparation and pharmaceutical compositions containing certain such compounds |
| CA1271477A (en) | 1983-11-18 | 1990-07-10 | John F. Gerster | 1h-imidazo[4,5-c]quinolin-4-amines |
| US4820508A (en) | 1987-06-23 | 1989-04-11 | Neutrogena Corporation | Skin protective composition |
| US4992478A (en) | 1988-04-04 | 1991-02-12 | Warner-Lambert Company | Antiinflammatory skin moisturizing composition and method of preparing same |
| US4938949A (en) | 1988-09-12 | 1990-07-03 | University Of New York | Treatment of damaged bone marrow and dosage units therefor |
| US5736553A (en) | 1988-12-15 | 1998-04-07 | Riker Laboratories, Inc. | Topical formulations and transdermal delivery systems containing 1-isobutyl-1H-imidazo 4,5-C!quinolin-4-amine |
| US5238944A (en) | 1988-12-15 | 1993-08-24 | Riker Laboratories, Inc. | Topical formulations and transdermal delivery systems containing 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine |
| US4929624A (en) | 1989-03-23 | 1990-05-29 | Minnesota Mining And Manufacturing Company | Olefinic 1H-imidazo(4,5-c)quinolin-4-amines |
| US5037986A (en) | 1989-03-23 | 1991-08-06 | Minnesota Mining And Manufacturing Company | Olefinic 1H-imidazo[4,5-c]quinolin-4-amines |
| NZ232740A (en) | 1989-04-20 | 1992-06-25 | Riker Laboratories Inc | Solution for parenteral administration comprising a 1h-imidazo(4,5-c) quinolin-4-amine derivative, an acid and a tonicity adjuster |
| DK0553202T3 (da) | 1990-10-05 | 1995-07-03 | Minnesota Mining & Mfg | Fremgangsmåde til fremstilling af imidazo(4,5-c)quinolin-4-aminer |
| US5175296A (en) | 1991-03-01 | 1992-12-29 | Minnesota Mining And Manufacturing Company | Imidazo[4,5-c]quinolin-4-amines and processes for their preparation |
| IL105325A (en) | 1992-04-16 | 1996-11-14 | Minnesota Mining & Mfg | Immunogen/vaccine adjuvant composition |
| US5395937A (en) | 1993-01-29 | 1995-03-07 | Minnesota Mining And Manufacturing Company | Process for preparing quinoline amines |
| US5352784A (en) | 1993-07-15 | 1994-10-04 | Minnesota Mining And Manufacturing Company | Fused cycloalkylimidazopyridines |
| US5648516A (en) | 1994-07-20 | 1997-07-15 | Minnesota Mining And Manufacturing Company | Fused cycloalkylimidazopyridines |
| US5525606A (en) | 1994-08-01 | 1996-06-11 | The United States Of America As Represented By The Department Of Health And Human Services | Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines |
| DE19505168A1 (de) | 1995-02-16 | 1996-08-22 | Boehringer Mannheim Gmbh | Spezifische Lipidkonjugate von Nucleosid-Diphosphonaten und deren Verwendung als Arzneimittel |
| US5624677A (en) | 1995-06-13 | 1997-04-29 | Pentech Pharmaceuticals, Inc. | Controlled release of drugs delivered by sublingual or buccal administration |
| US5741908A (en) | 1996-06-21 | 1998-04-21 | Minnesota Mining And Manufacturing Company | Process for reparing imidazoquinolinamines |
| US5693811A (en) | 1996-06-21 | 1997-12-02 | Minnesota Mining And Manufacturing Company | Process for preparing tetrahdroimidazoquinolinamines |
| DE19637209B4 (de) | 1996-09-12 | 2006-12-14 | Siemens Ag | Verfahren zum Steuern des Antriebsstrangs eines Kraftfahrzeugs und integrierte Antriebsstrangsteuerung |
| DE69735292T2 (de) | 1996-10-25 | 2006-10-19 | Gilead Sciences, Inc., Foster City | Gefaesszellen wachstumsfaktor (vegf) nukleinsäureligand-komplexe |
| KR100518903B1 (ko) | 1996-10-25 | 2005-10-06 | 미네소타 마이닝 앤드 매뉴팩춰링 캄파니 | Th2 매개 질병 및 관련 질병의 치료용 면역 반응 조절 화합물 |
| JPH10298181A (ja) | 1997-04-25 | 1998-11-10 | Sumitomo Pharmaceut Co Ltd | タイプ2ヘルパーt細胞選択的免疫応答抑制剤 |
| WO1999024432A1 (fr) | 1997-11-12 | 1999-05-20 | Mitsubishi Chemical Corporation | Derives de purine et medicament les renfermant en tant qu'ingredient actif |
| NZ504800A (en) | 1997-11-28 | 2001-10-26 | Sumitomo Pharma | 6-Amino-9-benzyl-8-hydroxy-purine derivatives and interferon inducers, antiviral agents, anticancer agents and therapeutic agents for immunologic diseases thereof |
| JP4189048B2 (ja) | 1997-12-26 | 2008-12-03 | 大日本住友製薬株式会社 | 複素環化合物 |
| US7001609B1 (en) | 1998-10-02 | 2006-02-21 | Regents Of The University Of Minnesota | Mucosal originated drug delivery systems and animal applications |
| TR200101943T2 (tr) | 1999-01-08 | 2002-04-22 | 3M Innovative Properties Company | Bir immun cevap modifayeri ile mukoza ile ilgili durumların tedavisine yönelik formülasyonlar ve metodlar. |
| US20020058674A1 (en) | 1999-01-08 | 2002-05-16 | Hedenstrom John C. | Systems and methods for treating a mucosal surface |
| US6486168B1 (en) | 1999-01-08 | 2002-11-26 | 3M Innovative Properties Company | Formulations and methods for treatment of mucosal associated conditions with an immune response modifier |
| CZ27399A3 (cs) | 1999-01-26 | 2000-08-16 | Ústav Experimentální Botaniky Av Čr | Substituované dusíkaté heterocyklické deriváty, způsob jejich přípravy, tyto deriváty pro použití jako léčiva, farmaceutická kompozice a kombinovaný farmaceutický přípravek tyto deriváty obsahující a použití těchto derivátů pro výrobu léčiv |
| ATE345349T1 (de) | 1999-12-17 | 2006-12-15 | Ariad Pharma Inc | Purinderivate |
| DE60028253T2 (de) | 1999-12-17 | 2007-03-08 | Ariad Pharmaceuticals, Inc., Cambridge | Neue purine |
| ATE322494T1 (de) | 2000-01-07 | 2006-04-15 | Universitaire Instelling Antwe | Purin derivate, ihre herstellung und verwendung |
| US6733764B2 (en) | 2000-06-14 | 2004-05-11 | Alain Martin | Immunostimulator anti-cancer compounds and methods for their use in the treatment of cancer |
| AU2002212273B2 (en) | 2000-09-15 | 2007-06-14 | Aaron Diamond Aids Research Centre | System and method for optimizing drug therapy for the treatment of diseases |
| GB0023008D0 (en) | 2000-09-20 | 2000-11-01 | Glaxo Group Ltd | Improvements in vaccination |
| AU2002211602A1 (en) | 2000-10-11 | 2002-04-22 | Johns Hopkins University | Polymer controlled delivery of a therapeutic agent |
| US20020127224A1 (en) | 2001-03-02 | 2002-09-12 | James Chen | Use of photoluminescent nanoparticles for photodynamic therapy |
| ATE348097T1 (de) | 2001-04-09 | 2007-01-15 | Chiron Corp | Guanidinoverbindungen als melanocortin-4-rezeptor (mc4-r) agonisten |
| US7157465B2 (en) | 2001-04-17 | 2007-01-02 | Dainippon Simitomo Pharma Co., Ltd. | Adenine derivatives |
| EP1572067A4 (en) | 2001-05-18 | 2009-05-13 | Sirna Therapeutics Inc | CONJUGATES AND COMPOSITIONS FOR CELLULAR RELEASE |
| DE60206756T2 (de) | 2001-06-29 | 2006-07-13 | CV Therapeutics, Inc., Palo Alto | Purin derivate als a2b adenosin rezeptor antagonisten |
| US7241890B2 (en) | 2001-10-30 | 2007-07-10 | Conforma Therapeutics Corporation | Purine analogs having HSP90-inhibiting activity |
| GB0206461D0 (en) | 2002-03-19 | 2002-05-01 | Glaxo Group Ltd | Improvements in vaccination |
| NZ538812A (en) | 2002-08-15 | 2009-02-28 | 3M Innovative Properties Co | Immunostimulatory compositions and methods of stimulating an immune response |
| AU2003271064B2 (en) | 2002-09-27 | 2010-06-17 | Dainippon Sumitomo Pharma Co., Ltd. | Novel adenine compound and use thereof |
| JP2004137157A (ja) | 2002-10-16 | 2004-05-13 | Sumitomo Pharmaceut Co Ltd | 新規アデニン誘導体を有効成分として含有する医薬 |
| CA2512161A1 (en) | 2003-01-28 | 2004-08-12 | Shanghai Sunway Biotech Co., Ltd | Hyperthermia oncolysis co-therapy |
| US20040265351A1 (en) | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
| WO2005016235A2 (en) | 2003-04-14 | 2005-02-24 | The Regents Of The University Of California | Combined use of impdh inhibitors with toll-like receptor agonists |
| US20050059613A1 (en) | 2003-07-08 | 2005-03-17 | Bahram Memarzadeh | Compositions and methods for the enhanced uptake of therapeutic agents through the bladder epithelium |
| WO2005020892A2 (en) | 2003-08-08 | 2005-03-10 | Mitochroma Research, Inc. | Pharmaceutical compositions and methods for metabolic modulation |
| EP1667694B1 (en) | 2003-09-05 | 2010-04-28 | Anadys Pharmaceuticals, Inc. | Tlr7 ligands for the treatment of hepatitis c |
| JP2005089334A (ja) | 2003-09-12 | 2005-04-07 | Sumitomo Pharmaceut Co Ltd | 8−ヒドロキシアデニン化合物 |
| KR20060070572A (ko) | 2003-09-18 | 2006-06-23 | 콘포마 세러퓨틱스 코포레이션 | Hsp90-저해제로서의 신규 헤테로시클릭 화합물 |
| FR2863890B1 (fr) * | 2003-12-19 | 2006-03-24 | Aventis Pasteur | Composition immunostimulante |
| JP2007526322A (ja) | 2004-03-02 | 2007-09-13 | マサチューセッツ インスティテュート オブ テクノロジー | ナノセル薬物送達系 |
| WO2005092893A1 (ja) | 2004-03-26 | 2005-10-06 | Dainippon Sumitomo Pharma Co., Ltd. | 9置換−8−オキソアデニン化合物 |
| US20070225303A1 (en) * | 2004-03-26 | 2007-09-27 | Haruhisa Ogita | 8-Oxoadenine Compound |
| CA2587676A1 (en) | 2004-11-19 | 2006-05-26 | Institut Gustave Roussy | Improved treatment of cancer by double-stranded rna |
| PT1819230E (pt) | 2004-12-07 | 2012-08-07 | Univ Miami | Micropartículas derivadas de células vermelhas como agentes hemostáticos para o controlo da hemorragia e para o tratamento de patologias hemorrágicas |
| DK1879893T3 (da) | 2005-03-21 | 2010-09-13 | Ferrer Int | Fremgangsmåde til fremstilling af 1-substituerede 1H-imidazo[4,5-c]quinolin-4-aminforbindelser og mellemprodukter dertil |
| US20070292418A1 (en) | 2005-04-26 | 2007-12-20 | Eisai Co., Ltd. | Compositions and methods for immunotherapy |
| ES2577514T3 (es) * | 2005-08-22 | 2016-07-15 | The Regents Of The University Of California | Antagonistas de TLR |
| WO2007034917A1 (ja) * | 2005-09-22 | 2007-03-29 | Dainippon Sumitomo Pharma Co., Ltd. | 新規なアデニン化合物 |
| EP1939202A4 (en) | 2005-09-22 | 2010-06-16 | Dainippon Sumitomo Pharma Co | NEW ADENINE CONNECTION |
| KR20080059595A (ko) | 2005-09-27 | 2008-06-30 | 콜리 파마슈티칼 게엠베하 | 어댑터 올리고뉴클레오티드를 사용하는 tlr-매개 면역반응의 조절 |
| US20070100146A1 (en) | 2005-11-03 | 2007-05-03 | Trevor Dzwiniel | Process for the preparation of imidazo[4,5-c]-quinolin-4-amines |
| EP2029597A4 (en) | 2006-05-31 | 2011-11-23 | Univ California | purine analogs |
| EP2038290B1 (en) | 2006-07-07 | 2013-09-04 | Gilead Sciences, Inc. | Modulators of toll-like receptor 7 |
| TW200831104A (en) | 2006-10-04 | 2008-08-01 | Pharmacopeia Inc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| US7902187B2 (en) | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| ES2552471T3 (es) | 2007-02-07 | 2015-11-30 | The Regents Of The University Of California | Conjugados de agonistas de TLR sintéticos y usos de los mismos |
| CA2691444C (en) | 2007-06-29 | 2016-06-14 | Gilead Sciences, Inc. | Purine derivatives and their use as modulators of toll-like receptor 7 |
| JP2011500716A (ja) | 2007-10-16 | 2011-01-06 | ギリアード・パロ・アルト・インコーポレイテッド | A3アデノシン受容体アンタゴニスト |
| EA201001264A1 (ru) | 2008-02-07 | 2011-04-29 | Дзе Регентс Оф Дзе Юниверсити Оф Калифорния | Способ лечения заболеваний мочевого пузыря с помощью активатора tlr7 |
| WO2010088924A1 (en) | 2009-02-06 | 2010-08-12 | Telormedix Sa | Pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration |
| KR20110117705A (ko) | 2009-02-11 | 2011-10-27 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 톨-유사 수용체 조정제 및 질병의 치료 |
| US8962652B2 (en) | 2009-10-22 | 2015-02-24 | Gilead Sciences, Inc. | Derivatives of purine or deazapurine useful for the treatment of (inter alia) viral infections |
| WO2011134669A1 (en) | 2010-04-30 | 2011-11-03 | Telormedix Sa | Methods for inducing an immune response |
| US20130202629A1 (en) | 2010-04-30 | 2013-08-08 | The Regents Of The University Of California | Uses of phospholipid conjugates of synthetic tlr7 agonists |
| NZ603155A (en) | 2010-04-30 | 2014-06-27 | Telormedix Sa | Phospholipid drug analogs |
| ES2458355T3 (es) | 2010-09-01 | 2014-05-05 | Novartis Ag | Adsorción de inmunopotenciadores sobre sales metálicas insolubles |
| US20120083473A1 (en) | 2010-09-21 | 2012-04-05 | Johanna Holldack | Treatment of conditions by toll-like receptor modulators |
-
2008
- 2008-02-07 ES ES12004181.9T patent/ES2552471T3/es active Active
- 2008-02-07 US US12/027,960 patent/US8357374B2/en active Active
- 2008-02-07 EP EP08799591.6A patent/EP2125007B9/en active Active
- 2008-02-07 PL PL12004181T patent/PL2510946T3/pl unknown
- 2008-02-07 EA EA200901078A patent/EA019151B1/ru unknown
- 2008-02-07 JP JP2009549102A patent/JP5425642B2/ja not_active Expired - Fee Related
- 2008-02-07 DK DK12004181.9T patent/DK2510946T3/da active
- 2008-02-07 AU AU2008227128A patent/AU2008227128B2/en active Active
- 2008-02-07 HU HUE12004181A patent/HUE025555T2/en unknown
- 2008-02-07 KR KR1020097018499A patent/KR20090109121A/ko not_active Ceased
- 2008-02-07 WO PCT/US2008/001631 patent/WO2008115319A2/en not_active Ceased
- 2008-02-07 SI SI200831521T patent/SI2510946T1/sl unknown
- 2008-02-07 EP EP12004181.9A patent/EP2510946B1/en active Active
- 2008-02-07 PL PL08799591T patent/PL2125007T3/pl unknown
- 2008-02-07 CA CA002677733A patent/CA2677733A1/en not_active Abandoned
- 2008-02-07 CN CN2008800115258A patent/CN101790380B/zh active Active
- 2008-02-07 PT PT120041819T patent/PT2510946E/pt unknown
- 2008-02-07 ES ES08799591.6T patent/ES2456964T3/es active Active
-
2009
- 2009-08-05 IL IL200240A patent/IL200240A/en active IP Right Grant
- 2009-09-02 ZA ZA2009/06094A patent/ZA200906094B/en unknown
-
2013
- 2013-01-08 US US13/736,545 patent/US8790655B2/en active Active
- 2013-03-22 JP JP2013059721A patent/JP2013127004A/ja not_active Withdrawn
-
2014
- 2014-06-19 US US14/309,245 patent/US9050376B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2510946T3 (da) | Konjugater af syntetiske tlr-agonister og anvendelser deraf | |
| US20130202629A1 (en) | Uses of phospholipid conjugates of synthetic tlr7 agonists | |
| US9359360B2 (en) | TLR agonists | |
| HK1177886B (en) | Conjugates of synthetic tlr agonists and uses therefor | |
| HK1138767B (en) | Conjugates of synthetic tlr agonists and uses therefor | |
| BRPI0807196B1 (pt) | Compostos 6-amino-8-hidróxipurin-9-ilbenzil substituídos, e, usos dos mesmos | |
| HK1126114A (en) | Tlr agonists |