ES2368926T3 - Hosm de unión a inmunoglobulina. - Google Patents

Info

Publication number

ES2368926T3

ES2368926T3 ES05733043T ES05733043T ES2368926T3 ES 2368926 T3 ES2368926 T3 ES 2368926T3 ES 05733043 T ES05733043 T ES 05733043T ES 05733043 T ES05733043 T ES 05733043T ES 2368926 T3 ES2368926 T3 ES 2368926T3

Authority

ES

Spain

Prior art keywords

antibody

osm

seq

human

antibodies

Prior art date

2004-03-30

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Lifetime

Links

• Espacenet
• Global Dossier
• Discuss

• 108060003951 Immunoglobulin Proteins 0.000 title description 16
• 102000018358 immunoglobulin Human genes 0.000 title description 16
• 230000027455 binding Effects 0.000 claims abstract description 189
• 239000012634 fragment Substances 0.000 claims abstract description 120
• 239000000427 antigen Substances 0.000 claims abstract description 99
• 108091007433 antigens Proteins 0.000 claims abstract description 99
• 102000036639 antigens Human genes 0.000 claims abstract description 99
• 241000282414 Homo sapiens Species 0.000 claims description 162
• 210000004027 cell Anatomy 0.000 claims description 158
• 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 claims description 122
• 101710152369 Interleukin-6 receptor subunit beta Proteins 0.000 claims description 101
• 230000003993 interaction Effects 0.000 claims description 74
• 238000011282 treatment Methods 0.000 claims description 60
• 239000013598 vector Substances 0.000 claims description 56
• 241001529936 Murinae Species 0.000 claims description 50
• 239000013612 plasmid Substances 0.000 claims description 49
• 102000040430 polynucleotide Human genes 0.000 claims description 39
• 108091033319 polynucleotide Proteins 0.000 claims description 39
• 239000002157 polynucleotide Substances 0.000 claims description 39
• 239000008194 pharmaceutical composition Substances 0.000 claims description 34
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 33
• 201000008482 osteoarthritis Diseases 0.000 claims description 25
• 238000004519 manufacturing process Methods 0.000 claims description 24
• 230000000903 blocking effect Effects 0.000 claims description 21
• 239000003814 drug Substances 0.000 claims description 15
• 201000004681 Psoriasis Diseases 0.000 claims description 10
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• 239000002699 waste material Substances 0.000 claims description 7
• 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 6
• 210000004962 mammalian cell Anatomy 0.000 claims description 6
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
• 241000282553 Macaca Species 0.000 claims description 5
• 241000288906 Primates Species 0.000 claims description 4
• 230000002101 lytic effect Effects 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 claims description 3
• 241000700159 Rattus Species 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 238000012258 culturing Methods 0.000 claims description 2
• 102000004140 Oncostatin M Human genes 0.000 description 329
• 108090000630 Oncostatin M Proteins 0.000 description 329
• 101000992170 Homo sapiens Oncostatin-M Proteins 0.000 description 161
• 102000043703 human OSM Human genes 0.000 description 161
• 230000001225 therapeutic effect Effects 0.000 description 99
• 238000000034 method Methods 0.000 description 83
• 238000002965 ELISA Methods 0.000 description 78
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 70
• 238000003556 assay Methods 0.000 description 56
• 230000005764 inhibitory process Effects 0.000 description 51
• 201000010099 disease Diseases 0.000 description 49
• 210000002966 serum Anatomy 0.000 description 39
• 239000002609 medium Substances 0.000 description 35
• 108090000623 proteins and genes Proteins 0.000 description 30
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 27
• 238000010276 construction Methods 0.000 description 27
• 230000014509 gene expression Effects 0.000 description 27
• 108020004414 DNA Proteins 0.000 description 25
• 102100021747 Leukemia inhibitory factor receptor Human genes 0.000 description 25
• 239000000872 buffer Substances 0.000 description 25
• 239000000499 gel Substances 0.000 description 25
• 102000005962 receptors Human genes 0.000 description 25
• 108020003175 receptors Proteins 0.000 description 25
• 238000012360 testing method Methods 0.000 description 25
• 101001042362 Homo sapiens Leukemia inhibitory factor receptor Proteins 0.000 description 24
• 238000010367 cloning Methods 0.000 description 23
• 239000000203 mixture Substances 0.000 description 23
• 238000006386 neutralization reaction Methods 0.000 description 22
• 239000000047 product Substances 0.000 description 22
• 241000699666 Mus <mouse, genus> Species 0.000 description 21
• 208000035475 disorder Diseases 0.000 description 21
• 230000000694 effects Effects 0.000 description 21
• 239000006228 supernatant Substances 0.000 description 21
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 20
• 102000004127 Cytokines Human genes 0.000 description 20
• 108090000695 Cytokines Proteins 0.000 description 20
• 101000599056 Homo sapiens Interleukin-6 receptor subunit beta Proteins 0.000 description 20
• 102000004889 Interleukin-6 Human genes 0.000 description 20
• 108090001005 Interleukin-6 Proteins 0.000 description 20
• 238000000746 purification Methods 0.000 description 20
• 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 19
• 241000699670 Mus sp. Species 0.000 description 19
• 102100024952 Protein CBFA2T1 Human genes 0.000 description 19
• 206010003246 arthritis Diseases 0.000 description 19
• 230000002860 competitive effect Effects 0.000 description 19
• 229940100601 interleukin-6 Drugs 0.000 description 19
• 235000018102 proteins Nutrition 0.000 description 19
• 102000004169 proteins and genes Human genes 0.000 description 19
• 210000001179 synovial fluid Anatomy 0.000 description 19
• 108010076504 Protein Sorting Signals Proteins 0.000 description 18
• 229960000723 ampicillin Drugs 0.000 description 18
• AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 18
• 101000586302 Homo sapiens Oncostatin-M-specific receptor subunit beta Proteins 0.000 description 17
• 102100030098 Oncostatin-M-specific receptor subunit beta Human genes 0.000 description 17
• 125000003275 alpha amino acid group Chemical group 0.000 description 17
• 230000015572 biosynthetic process Effects 0.000 description 17
• 239000000243 solution Substances 0.000 description 17
• 239000013604 expression vector Substances 0.000 description 16
• 210000004408 hybridoma Anatomy 0.000 description 16
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 15
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 15
• 230000008569 process Effects 0.000 description 15
• 230000002441 reversible effect Effects 0.000 description 15
• 230000003389 potentiating effect Effects 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• 238000003757 reverse transcription PCR Methods 0.000 description 13
• 238000004458 analytical method Methods 0.000 description 12
• 238000001514 detection method Methods 0.000 description 12
• 230000001965 increasing effect Effects 0.000 description 12
• 210000000440 neutrophil Anatomy 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
• 239000005557 antagonist Substances 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 11
• 210000002950 fibroblast Anatomy 0.000 description 11
• 230000006870 function Effects 0.000 description 11
• 239000001963 growth medium Substances 0.000 description 11
• 230000002757 inflammatory effect Effects 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• 230000028327 secretion Effects 0.000 description 11
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 10
• 210000004369 blood Anatomy 0.000 description 10
• 239000008280 blood Substances 0.000 description 10
• 238000011161 development Methods 0.000 description 10
• 230000018109 developmental process Effects 0.000 description 10
• 210000002889 endothelial cell Anatomy 0.000 description 10
• 210000001503 joint Anatomy 0.000 description 10
• 238000010839 reverse transcription Methods 0.000 description 10
• 102000003390 tumor necrosis factor Human genes 0.000 description 10
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
• 238000012286 ELISA Assay Methods 0.000 description 9
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 9
• 210000001744 T-lymphocyte Anatomy 0.000 description 9
• 238000013459 approach Methods 0.000 description 9
• 230000002917 arthritic effect Effects 0.000 description 9
• 210000004556 brain Anatomy 0.000 description 9
• 238000010790 dilution Methods 0.000 description 9
• 239000012895 dilution Substances 0.000 description 9
• 230000013595 glycosylation Effects 0.000 description 9
• 238000006206 glycosylation reaction Methods 0.000 description 9
• 239000003550 marker Substances 0.000 description 9
• 230000003472 neutralizing effect Effects 0.000 description 9
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 9
• 241000283707 Capra Species 0.000 description 8
• 239000012636 effector Substances 0.000 description 8
• 238000005516 engineering process Methods 0.000 description 8
• 230000003902 lesion Effects 0.000 description 8
• 108090000765 processed proteins & peptides Proteins 0.000 description 8
• 230000035755 proliferation Effects 0.000 description 8
• 238000011084 recovery Methods 0.000 description 8
• 206010061218 Inflammation Diseases 0.000 description 7
• 108091034117 Oligonucleotide Proteins 0.000 description 7
• 206010035226 Plasma cell myeloma Diseases 0.000 description 7
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
• 238000002835 absorbance Methods 0.000 description 7
• 210000003719 b-lymphocyte Anatomy 0.000 description 7
• 239000002299 complementary DNA Substances 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 239000012149 elution buffer Substances 0.000 description 7
• 230000003053 immunization Effects 0.000 description 7
• 230000004054 inflammatory process Effects 0.000 description 7
• 238000005259 measurement Methods 0.000 description 7
• 230000035772 mutation Effects 0.000 description 7
• 201000000050 myeloid neoplasm Diseases 0.000 description 7
• 239000000523 sample Substances 0.000 description 7
• 238000012163 sequencing technique Methods 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• 230000009466 transformation Effects 0.000 description 7
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 6
• 102000000589 Interleukin-1 Human genes 0.000 description 6
• 108010002352 Interleukin-1 Proteins 0.000 description 6
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 6
• 241000282567 Macaca fascicularis Species 0.000 description 6
• 241000219061 Rheum Species 0.000 description 6
• 229920002684 Sepharose Polymers 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• 210000000988 bone and bone Anatomy 0.000 description 6
• 210000000845 cartilage Anatomy 0.000 description 6
• 230000000295 complement effect Effects 0.000 description 6
• 230000001419 dependent effect Effects 0.000 description 6
• 230000008021 deposition Effects 0.000 description 6
• 230000004927 fusion Effects 0.000 description 6
• 239000003102 growth factor Substances 0.000 description 6
• 238000002649 immunization Methods 0.000 description 6
• 229940072221 immunoglobulins Drugs 0.000 description 6
• 238000011534 incubation Methods 0.000 description 6
• 208000027866 inflammatory disease Diseases 0.000 description 6
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
• 125000005647 linker group Chemical group 0.000 description 6
• 210000004698 lymphocyte Anatomy 0.000 description 6
• 210000002540 macrophage Anatomy 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 229960000485 methotrexate Drugs 0.000 description 6
• 210000002569 neuron Anatomy 0.000 description 6
• 230000035945 sensitivity Effects 0.000 description 6
• 210000003491 skin Anatomy 0.000 description 6
• 230000000638 stimulation Effects 0.000 description 6
• 238000001890 transfection Methods 0.000 description 6
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 5
• 208000024827 Alzheimer disease Diseases 0.000 description 5
• 108010008165 Etanercept Proteins 0.000 description 5
• 102000003886 Glycoproteins Human genes 0.000 description 5
• 108090000288 Glycoproteins Proteins 0.000 description 5
• 238000002123 RNA extraction Methods 0.000 description 5
• 239000008049 TAE buffer Substances 0.000 description 5
• 241000700605 Viruses Species 0.000 description 5
• 238000009825 accumulation Methods 0.000 description 5
• HGEVZDLYZYVYHD-UHFFFAOYSA-N acetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound CC(O)=O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O HGEVZDLYZYVYHD-UHFFFAOYSA-N 0.000 description 5
• 238000001042 affinity chromatography Methods 0.000 description 5
• 238000004113 cell culture Methods 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 230000001684 chronic effect Effects 0.000 description 5
• 230000006378 damage Effects 0.000 description 5
• 208000037765 diseases and disorders Diseases 0.000 description 5
• 239000003623 enhancer Substances 0.000 description 5
• ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 5
• 229960005542 ethidium bromide Drugs 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 238000000605 extraction Methods 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 238000011068 loading method Methods 0.000 description 5
• 210000004072 lung Anatomy 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 229920001817 Agar Polymers 0.000 description 4
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 4
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
• 241000282693 Cercopithecidae Species 0.000 description 4
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 4
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 206010063560 Excessive granulation tissue Diseases 0.000 description 4
• 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 4
• 229920001213 Polysorbate 20 Polymers 0.000 description 4
• 241000283984 Rodentia Species 0.000 description 4
• 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 4
• 239000008272 agar Substances 0.000 description 4
• 239000011543 agarose gel Substances 0.000 description 4
• 235000001014 amino acid Nutrition 0.000 description 4
• 150000001413 amino acids Chemical class 0.000 description 4
• 210000001188 articular cartilage Anatomy 0.000 description 4
• 230000003143 atherosclerotic effect Effects 0.000 description 4
• 230000003115 biocidal effect Effects 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 208000037976 chronic inflammation Diseases 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 239000012228 culture supernatant Substances 0.000 description 4
• 230000004069 differentiation Effects 0.000 description 4
• 210000003038 endothelium Anatomy 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 210000003527 eukaryotic cell Anatomy 0.000 description 4
• 239000012091 fetal bovine serum Substances 0.000 description 4
• 210000001126 granulation tissue Anatomy 0.000 description 4
• 230000005847 immunogenicity Effects 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 210000003292 kidney cell Anatomy 0.000 description 4
• 239000011159 matrix material Substances 0.000 description 4
• 210000001616 monocyte Anatomy 0.000 description 4
• 201000006417 multiple sclerosis Diseases 0.000 description 4
• 230000002018 overexpression Effects 0.000 description 4
• 230000007170 pathology Effects 0.000 description 4
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
• 230000002787 reinforcement Effects 0.000 description 4
• 230000010076 replication Effects 0.000 description 4
• 239000011550 stock solution Substances 0.000 description 4
• 210000001258 synovial membrane Anatomy 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 230000009885 systemic effect Effects 0.000 description 4
• 239000012096 transfection reagent Substances 0.000 description 4
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 4
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
• 102100028892 Cardiotrophin-1 Human genes 0.000 description 3
• 102100024746 Dihydrofolate reductase Human genes 0.000 description 3
• 241000588724 Escherichia coli Species 0.000 description 3
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
• 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 3
• 102000004877 Insulin Human genes 0.000 description 3
• 108090001061 Insulin Proteins 0.000 description 3
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 3
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 3
• 102220485208 Myelin proteolipid protein_L46R_mutation Human genes 0.000 description 3
• 208000002193 Pain Diseases 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 102220534532 Protein quaking_Q38K_mutation Human genes 0.000 description 3
• 108010067787 Proteoglycans Proteins 0.000 description 3
• 102000016611 Proteoglycans Human genes 0.000 description 3
• 108091036333 Rapid DNA Proteins 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 108010000499 Thromboplastin Proteins 0.000 description 3
• 102100030859 Tissue factor Human genes 0.000 description 3
• 239000007984 Tris EDTA buffer Substances 0.000 description 3
• 238000005273 aeration Methods 0.000 description 3
• 235000004279 alanine Nutrition 0.000 description 3
• 230000033115 angiogenesis Effects 0.000 description 3
• 230000001580 bacterial effect Effects 0.000 description 3
• 229960000074 biopharmaceutical Drugs 0.000 description 3
• 108010041776 cardiotrophin 1 Proteins 0.000 description 3
• 230000008355 cartilage degradation Effects 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 238000009833 condensation Methods 0.000 description 3
• 230000005494 condensation Effects 0.000 description 3
• 108020001096 dihydrofolate reductase Proteins 0.000 description 3
• 238000006471 dimerization reaction Methods 0.000 description 3
• 229940073621 enbrel Drugs 0.000 description 3
• 210000003979 eosinophil Anatomy 0.000 description 3
• 210000002744 extracellular matrix Anatomy 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 229940048921 humira Drugs 0.000 description 3
• 238000004191 hydrophobic interaction chromatography Methods 0.000 description 3
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
• 230000001969 hypertrophic effect Effects 0.000 description 3
• 230000006698 induction Effects 0.000 description 3
• 230000008595 infiltration Effects 0.000 description 3
• 238000001764 infiltration Methods 0.000 description 3
• 229940125396 insulin Drugs 0.000 description 3
• 238000005304 joining Methods 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 238000012423 maintenance Methods 0.000 description 3
• 210000003622 mature neutrocyte Anatomy 0.000 description 3
• 208000004296 neuralgia Diseases 0.000 description 3
• 208000021722 neuropathic pain Diseases 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 238000011533 pre-incubation Methods 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 230000001185 psoriatic effect Effects 0.000 description 3
• 230000007115 recruitment Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 102200086451 rs16948978 Human genes 0.000 description 3
• 102200082919 rs35857380 Human genes 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 150000003431 steroids Chemical class 0.000 description 3
• 229960005322 streptomycin Drugs 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 235000011149 sulphuric acid Nutrition 0.000 description 3
• 238000004114 suspension culture Methods 0.000 description 3
• 230000009261 transgenic effect Effects 0.000 description 3
• 230000032258 transport Effects 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• 239000011534 wash buffer Substances 0.000 description 3
• GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 2
• UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 2
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
• 102000013563 Acid Phosphatase Human genes 0.000 description 2
• 108010051457 Acid Phosphatase Proteins 0.000 description 2
• 206010048998 Acute phase reaction Diseases 0.000 description 2
• 102000011767 Acute-Phase Proteins Human genes 0.000 description 2
• 108010062271 Acute-Phase Proteins Proteins 0.000 description 2
• 229920000936 Agarose Polymers 0.000 description 2
• 208000036487 Arthropathies Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 2
• 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 2
• 108020004635 Complementary DNA Proteins 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• 241000701022 Cytomegalovirus Species 0.000 description 2
• 206010012438 Dermatitis atopic Diseases 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 241000196324 Embryophyta Species 0.000 description 2
• 108010049003 Fibrinogen Proteins 0.000 description 2
• 102000008946 Fibrinogen Human genes 0.000 description 2
• 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 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
• 206010065390 Inflammatory pain Diseases 0.000 description 2
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 2
• 208000012659 Joint disease Diseases 0.000 description 2
• 208000007766 Kaposi sarcoma Diseases 0.000 description 2
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• 102000003960 Ligases Human genes 0.000 description 2
• 108090000364 Ligases Proteins 0.000 description 2
• 241000699660 Mus musculus Species 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 2
• 208000008558 Osteophyte Diseases 0.000 description 2
• 102000016979 Other receptors Human genes 0.000 description 2
• 102100040460 P2X purinoceptor 3 Human genes 0.000 description 2
• 101710189970 P2X purinoceptor 3 Proteins 0.000 description 2
• 238000012408 PCR amplification Methods 0.000 description 2
• 206010057249 Phagocytosis Diseases 0.000 description 2
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 2
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
• 241000714474 Rous sarcoma virus Species 0.000 description 2
• 241000607720 Serratia Species 0.000 description 2
• 108010090804 Streptavidin Proteins 0.000 description 2
• 201000009594 Systemic Scleroderma Diseases 0.000 description 2
• 206010042953 Systemic sclerosis Diseases 0.000 description 2
• 102000004338 Transferrin Human genes 0.000 description 2
• 108090000901 Transferrin Proteins 0.000 description 2
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 239000002250 absorbent Substances 0.000 description 2
• 230000002745 absorbent Effects 0.000 description 2
• 230000004658 acute-phase response Effects 0.000 description 2
• 229960002964 adalimumab Drugs 0.000 description 2
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 239000002870 angiogenesis inducing agent Substances 0.000 description 2
• 239000003435 antirheumatic agent Substances 0.000 description 2
• 201000008937 atopic dermatitis Diseases 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 239000012472 biological sample Substances 0.000 description 2
• 230000010072 bone remodeling Effects 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 150000001720 carbohydrates Chemical group 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• 229960003115 certolizumab pegol Drugs 0.000 description 2
• 238000012412 chemical coupling Methods 0.000 description 2
• 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 description 2
• 210000001612 chondrocyte Anatomy 0.000 description 2
• 230000006020 chronic inflammation Effects 0.000 description 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 150000001875 compounds Chemical class 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• 230000009260 cross reactivity Effects 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 108010017271 denileukin diftitox Proteins 0.000 description 2
• 230000029087 digestion Effects 0.000 description 2
• 239000002988 disease modifying antirheumatic drug Substances 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 230000003511 endothelial effect Effects 0.000 description 2
• 238000001976 enzyme digestion Methods 0.000 description 2
• 210000002919 epithelial cell Anatomy 0.000 description 2
• 230000003628 erosive effect Effects 0.000 description 2
• 229960000403 etanercept Drugs 0.000 description 2
• 201000010934 exostosis Diseases 0.000 description 2
• 229940012952 fibrinogen Drugs 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 230000016784 immunoglobulin production Effects 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 239000000411 inducer Substances 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 229960000598 infliximab Drugs 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
• 230000000366 juvenile effect Effects 0.000 description 2
• 210000002510 keratinocyte Anatomy 0.000 description 2
• 210000000265 leukocyte Anatomy 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 210000001165 lymph node Anatomy 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 210000000274 microglia Anatomy 0.000 description 2
• 238000002703 mutagenesis Methods 0.000 description 2
• 231100000350 mutagenesis Toxicity 0.000 description 2
• 108010068617 neonatal Fc receptor Proteins 0.000 description 2
• 230000002981 neuropathic effect Effects 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 235000015097 nutrients Nutrition 0.000 description 2
• 239000002751 oligonucleotide probe Substances 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000001717 pathogenic effect Effects 0.000 description 2
• 238000002823 phage display Methods 0.000 description 2
• 230000008782 phagocytosis Effects 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 229920001184 polypeptide Polymers 0.000 description 2
• XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 2
• ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
• 229940116176 remicade Drugs 0.000 description 2
• 108091008146 restriction endonucleases Proteins 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 102220168074 rs200199102 Human genes 0.000 description 2
• 102200156936 rs28934878 Human genes 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 239000013049 sediment Substances 0.000 description 2
• 230000009450 sialylation Effects 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 238000009097 single-agent therapy Methods 0.000 description 2
• 210000000952 spleen Anatomy 0.000 description 2
• 230000002269 spontaneous effect Effects 0.000 description 2
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 2
• 229960001940 sulfasalazine Drugs 0.000 description 2
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• 230000002195 synergetic effect Effects 0.000 description 2
• 210000005222 synovial tissue Anatomy 0.000 description 2
• 210000002437 synoviocyte Anatomy 0.000 description 2
• 201000004595 synovitis Diseases 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
• 230000031998 transcytosis Effects 0.000 description 2
• 239000012581 transferrin Substances 0.000 description 2
• 238000011830 transgenic mouse model Methods 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 210000001835 viscera Anatomy 0.000 description 2
• 230000029663 wound healing Effects 0.000 description 2
• DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
• RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
• WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
• OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• LPLLVINFLBSFRP-UHFFFAOYSA-N 2-methylamino-1-phenylpropan-1-one Chemical compound CNC(C)C(=O)C1=CC=CC=C1 LPLLVINFLBSFRP-UHFFFAOYSA-N 0.000 description 1
• OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
• VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
• SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
• OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
• ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 description 1
• 208000002874 Acne Vulgaris Diseases 0.000 description 1
• 102000007469 Actins Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 102000009027 Albumins Human genes 0.000 description 1
• 101710187573 Alcohol dehydrogenase 2 Proteins 0.000 description 1
• 101710133776 Alcohol dehydrogenase class-3 Proteins 0.000 description 1
• 208000037259 Amyloid Plaque Diseases 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 102000008076 Angiogenic Proteins Human genes 0.000 description 1
• 108010074415 Angiogenic Proteins Proteins 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 208000006820 Arthralgia Diseases 0.000 description 1
• 241000228212 Aspergillus Species 0.000 description 1
• 241000351920 Aspergillus nidulans Species 0.000 description 1
• 241000228245 Aspergillus niger Species 0.000 description 1
• 241000713842 Avian sarcoma virus Species 0.000 description 1
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
• 241000194108 Bacillus licheniformis Species 0.000 description 1
• 235000014469 Bacillus subtilis Nutrition 0.000 description 1
• 241000701822 Bovine papillomavirus Species 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
• 102000004631 Calcineurin Human genes 0.000 description 1
• 108010042955 Calcineurin Proteins 0.000 description 1
• 208000004434 Calcinosis Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 206010008096 Cerebral atrophy Diseases 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 241000282552 Chlorocebus aethiops Species 0.000 description 1
• 229920001287 Chondroitin sulfate Polymers 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
• 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 102000000503 Collagen Type II Human genes 0.000 description 1
• 108010041390 Collagen Type II Proteins 0.000 description 1
• 241001275954 Cortinarius caperatus Species 0.000 description 1
• 241000557626 Corvus corax Species 0.000 description 1
• 244000293323 Cosmos caudatus Species 0.000 description 1
• 235000005956 Cosmos caudatus Nutrition 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 101710081103 Cuticular glutathione peroxidase Proteins 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 108090000204 Dipeptidase 1 Proteins 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• 241000588914 Enterobacter Species 0.000 description 1
• 241000588921 Enterobacteriaceae Species 0.000 description 1
• 101710146739 Enterotoxin Proteins 0.000 description 1
• 102100023688 Eotaxin Human genes 0.000 description 1
• 101710139422 Eotaxin Proteins 0.000 description 1
• 241000588698 Erwinia Species 0.000 description 1
• 241000588722 Escherichia Species 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• 206010015866 Extravasation Diseases 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 208000028387 Felty syndrome Diseases 0.000 description 1
• 108010003471 Fetal Proteins Proteins 0.000 description 1
• 102000004641 Fetal Proteins Human genes 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 102000030595 Glucokinase Human genes 0.000 description 1
• 108010021582 Glucokinase Proteins 0.000 description 1
• 102100031132 Glucose-6-phosphate isomerase Human genes 0.000 description 1
• 108010070600 Glucose-6-phosphate isomerase Proteins 0.000 description 1
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 241000700721 Hepatitis B virus Species 0.000 description 1
• 208000009889 Herpes Simplex Diseases 0.000 description 1
• 102000005548 Hexokinase Human genes 0.000 description 1
• 108700040460 Hexokinases Proteins 0.000 description 1
• 241001272567 Hominoidea Species 0.000 description 1
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
• 101000725401 Homo sapiens Cytochrome c oxidase subunit 2 Proteins 0.000 description 1
• 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
• 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
• 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
• 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 1
• 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
• 101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 1
• 241000701109 Human adenovirus 2 Species 0.000 description 1
• 108010003272 Hyaluronate lyase Proteins 0.000 description 1
• 102000001974 Hyaluronidases Human genes 0.000 description 1
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
• 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
• 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
• 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
• 108090000172 Interleukin-15 Proteins 0.000 description 1
• 108050003558 Interleukin-17 Proteins 0.000 description 1
• 108090000171 Interleukin-18 Proteins 0.000 description 1
• 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
• 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
• 108090001007 Interleukin-8 Proteins 0.000 description 1
• SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
• 206010023204 Joint dislocation Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
• 238000002768 Kirby-Bauer method Methods 0.000 description 1
• 241000588748 Klebsiella Species 0.000 description 1
• 241000235649 Kluyveromyces Species 0.000 description 1
• 241000235058 Komagataella pastoris Species 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-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
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 101710142062 Leukemia inhibitory factor receptor Proteins 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
• 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
• 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
• 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
• 102000003792 Metallothionein Human genes 0.000 description 1
• 108090000157 Metallothionein Proteins 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 206010029113 Neovascularisation Diseases 0.000 description 1
• 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
• 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 108010067372 Pancreatic elastase Proteins 0.000 description 1
• 102000016387 Pancreatic elastase Human genes 0.000 description 1
• 241001111421 Pannus Species 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 241000282520 Papio Species 0.000 description 1
• 206010034016 Paronychia Diseases 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 108010090127 Periplasmic Proteins Proteins 0.000 description 1
• 102000001105 Phosphofructokinases Human genes 0.000 description 1
• 108010069341 Phosphofructokinases Proteins 0.000 description 1
• 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 1
• 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
• 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
• 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 1
• 241001505332 Polyomavirus sp. Species 0.000 description 1
• 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 1
• 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 1
• 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 241000588769 Proteus <enterobacteria> Species 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 240000001987 Pyrus communis Species 0.000 description 1
• 108010011939 Pyruvate Decarboxylase Proteins 0.000 description 1
• 101000852966 Rattus norvegicus Interleukin-1 receptor-like 1 Proteins 0.000 description 1
• 208000012322 Raynaud phenomenon Diseases 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 108010073443 Ribi adjuvant Proteins 0.000 description 1
• 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
• 241000607142 Salmonella Species 0.000 description 1
• 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
• 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
• 206010058556 Serositis Diseases 0.000 description 1
• 241000607768 Shigella Species 0.000 description 1
• 102000003838 Sialyltransferases Human genes 0.000 description 1
• 108090000141 Sialyltransferases Proteins 0.000 description 1
• 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 102000013275 Somatomedins Human genes 0.000 description 1
• 241000187747 Streptomyces Species 0.000 description 1
• 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
• 108700012920 TNF Proteins 0.000 description 1
• 101150006914 TRP1 gene Proteins 0.000 description 1
• 108010025083 TRPV1 receptor Proteins 0.000 description 1
• 208000033878 Tertiary Lymphoid Structures Diseases 0.000 description 1
• 239000004098 Tetracycline Substances 0.000 description 1
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
• 102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 1
• 241001149964 Tolypocladium Species 0.000 description 1
• 108010033576 Transferrin Receptors Proteins 0.000 description 1
• 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
• 241000223259 Trichoderma Species 0.000 description 1
• UIRVSEPRMWDVEW-RNXOBYDBSA-N Trp-Tyr-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)N UIRVSEPRMWDVEW-RNXOBYDBSA-N 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 1
• 101150117115 V gene Proteins 0.000 description 1
• 241000700647 Variola virus Species 0.000 description 1
• 208000024248 Vascular System injury Diseases 0.000 description 1
• 208000012339 Vascular injury Diseases 0.000 description 1
• 206010053649 Vascular rupture Diseases 0.000 description 1
• 229930003316 Vitamin D Natural products 0.000 description 1
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
• 238000012452 Xenomouse strains Methods 0.000 description 1
• 241000235013 Yarrowia Species 0.000 description 1
• OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 229960005339 acitretin Drugs 0.000 description 1
• 206010000496 acne Diseases 0.000 description 1
• 206010069351 acute lung injury Diseases 0.000 description 1
• 230000003044 adaptive effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 230000009824 affinity maturation Effects 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 208000037883 airway inflammation Diseases 0.000 description 1
• 229960002459 alefacept Drugs 0.000 description 1
• IHUNBGSDBOWDMA-AQFIFDHZSA-N all-trans-acitretin Chemical compound COC1=CC(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1C IHUNBGSDBOWDMA-AQFIFDHZSA-N 0.000 description 1
• BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
• 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
• 235000011130 ammonium sulphate Nutrition 0.000 description 1
• 230000002491 angiogenic effect Effects 0.000 description 1
• 230000006427 angiogenic response Effects 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 238000005571 anion exchange chromatography Methods 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 238000011122 anti-angiogenic therapy Methods 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 230000000890 antigenic effect Effects 0.000 description 1
• 239000003430 antimalarial agent Substances 0.000 description 1
• 229940033495 antimalarials Drugs 0.000 description 1
• 208000007474 aortic aneurysm Diseases 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000003305 autocrine Effects 0.000 description 1
• 229960002170 azathioprine Drugs 0.000 description 1
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
• 244000052616 bacterial pathogen Species 0.000 description 1
• 229960004669 basiliximab Drugs 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
• 108010079452 beta Adrenergic Receptors Proteins 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
• 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
• 102000006635 beta-lactamase Human genes 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000002051 biphasic effect Effects 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 229960000590 celecoxib Drugs 0.000 description 1
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
• 230000005779 cell damage Effects 0.000 description 1
• 230000011712 cell development Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 208000037887 cell injury Diseases 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• 229960003677 chloroquine Drugs 0.000 description 1
• WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 229940059329 chondroitin sulfate Drugs 0.000 description 1
• 238000011210 chromatographic step Methods 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 230000004186 co-expression Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 230000037319 collagen production Effects 0.000 description 1
• 230000024203 complement activation Effects 0.000 description 1
• 238000005094 computer simulation Methods 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 230000006552 constitutive activation Effects 0.000 description 1
• 230000009133 cooperative interaction Effects 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 229940111134 coxibs Drugs 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 238000005138 cryopreservation Methods 0.000 description 1
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 229960002806 daclizumab Drugs 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 229960002923 denileukin diftitox Drugs 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 230000009266 disease activity Effects 0.000 description 1
• VZFDRQUWHOVFCA-UHFFFAOYSA-L disodium;2-sulfanylbutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(S)C([O-])=O VZFDRQUWHOVFCA-UHFFFAOYSA-L 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 229960000284 efalizumab Drugs 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 239000000147 enterotoxin Substances 0.000 description 1
• 231100000655 enterotoxin Toxicity 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 230000002327 eosinophilic effect Effects 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 229960002199 etretinate Drugs 0.000 description 1
• HQMNCQVAMBCHCO-DJRRULDNSA-N etretinate Chemical compound CCOC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C=C(OC)C(C)=C1C HQMNCQVAMBCHCO-DJRRULDNSA-N 0.000 description 1
• 230000036251 extravasation Effects 0.000 description 1
• 210000003414 extremity Anatomy 0.000 description 1
• 210000001508 eye Anatomy 0.000 description 1
• 238000000855 fermentation Methods 0.000 description 1
• 230000004151 fermentation Effects 0.000 description 1
• 230000035161 fibroblast apoptotic process Effects 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 238000009093 first-line therapy Methods 0.000 description 1
• 210000000497 foam cell Anatomy 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 108060003196 globin Proteins 0.000 description 1
• 102000018146 globin Human genes 0.000 description 1
• 229960002849 glucosamine sulfate Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
• 230000002414 glycolytic effect Effects 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 229940076085 gold Drugs 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 230000011132 hemopoiesis Effects 0.000 description 1
• 230000023597 hemostasis Effects 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• 238000005734 heterodimerization reaction Methods 0.000 description 1
• 229960001340 histamine Drugs 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 210000004124 hock Anatomy 0.000 description 1
• 239000012510 hollow fiber Substances 0.000 description 1
• 102000056549 human Fv Human genes 0.000 description 1
• 108700005872 human Fv Proteins 0.000 description 1
• 229960002773 hyaluronidase Drugs 0.000 description 1
• 201000010930 hyperostosis Diseases 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 230000016178 immune complex formation Effects 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 229940124589 immunosuppressive drug Drugs 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 230000004941 influx Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
• 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 239000001573 invertase Substances 0.000 description 1
• 235000011073 invertase Nutrition 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• -1 isocytochrome C Proteins 0.000 description 1
• 229960005280 isotretinoin Drugs 0.000 description 1
• 230000008407 joint function Effects 0.000 description 1
• 210000005067 joint tissue Anatomy 0.000 description 1
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
• 229940054136 kineret Drugs 0.000 description 1
• 210000003127 knee Anatomy 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000004922 lacquer Substances 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 238000011031 large-scale manufacturing process Methods 0.000 description 1
• 230000002045 lasting effect Effects 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 210000005265 lung cell Anatomy 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 230000013011 mating Effects 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 210000003071 memory t lymphocyte Anatomy 0.000 description 1
• 229960000901 mepacrine Drugs 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 238000001471 micro-filtration Methods 0.000 description 1
• 210000004925 microvascular endothelial cell Anatomy 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
• 210000000066 myeloid cell Anatomy 0.000 description 1
• 238000001728 nano-filtration Methods 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 210000003757 neuroblast Anatomy 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 210000001682 neurofibril Anatomy 0.000 description 1
• 230000007171 neuropathology Effects 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 230000003040 nociceptive effect Effects 0.000 description 1
• 229940121367 non-opioid analgesics Drugs 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 229940100027 ontak Drugs 0.000 description 1
• 239000000014 opioid analgesic Substances 0.000 description 1
• 229940005483 opioid analgesics Drugs 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 210000000963 osteoblast Anatomy 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229940055729 papain Drugs 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• 229960005489 paracetamol Drugs 0.000 description 1
• 239000013618 particulate matter Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007119 pathological manifestation Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 230000006320 pegylation Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 210000001322 periplasm Anatomy 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 101150009573 phoA gene Proteins 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 238000001126 phototherapy Methods 0.000 description 1
• 210000004180 plasmocyte Anatomy 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 229920001993 poloxamer 188 Polymers 0.000 description 1
• 229920002704 polyhistidine Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 230000030786 positive chemotaxis Effects 0.000 description 1
• 230000026341 positive regulation of angiogenesis Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 238000007639 printing Methods 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000002947 procoagulating effect Effects 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 239000003223 protective agent Substances 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• GPKJTRJOBQGKQK-UHFFFAOYSA-N quinacrine Chemical compound C1=C(OC)C=C2C(NC(C)CCCN(CC)CC)=C(C=CC(Cl)=C3)C3=NC2=C1 GPKJTRJOBQGKQK-UHFFFAOYSA-N 0.000 description 1
• 230000022983 regulation of cell cycle Effects 0.000 description 1
• 230000007363 regulatory process Effects 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• 229960000371 rofecoxib Drugs 0.000 description 1
• RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
• 102220047535 rs587783040 Human genes 0.000 description 1
• 210000004761 scalp Anatomy 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 238000010187 selection method Methods 0.000 description 1
• 210000001044 sensory neuron Anatomy 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 210000000717 sertoli cell Anatomy 0.000 description 1
• 239000012679 serum free medium Substances 0.000 description 1
• 239000004017 serum-free culture medium Substances 0.000 description 1
• 238000004904 shortening Methods 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 239000002356 single layer Substances 0.000 description 1
• 229950003804 siplizumab Drugs 0.000 description 1
• 238000002741 site-directed mutagenesis Methods 0.000 description 1
• 238000001542 size-exclusion chromatography Methods 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 201000010153 skin papilloma Diseases 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 210000001082 somatic cell Anatomy 0.000 description 1
• 230000010473 stable expression Effects 0.000 description 1
• 230000003068 static effect Effects 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 210000005065 subchondral bone plate Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000005737 synergistic response Effects 0.000 description 1
• 229960000565 tazarotene Drugs 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• 229960002180 tetracycline Drugs 0.000 description 1
• 229930101283 tetracycline Natural products 0.000 description 1
• 235000019364 tetracycline Nutrition 0.000 description 1
• 150000003522 tetracyclines Chemical class 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• 239000003104 tissue culture media Substances 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 229960000187 tissue plasminogen activator Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000012876 topography Methods 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 230000005030 transcription termination Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 102000057702 transmembrane signaling receptor Human genes 0.000 description 1
• 108700011013 transmembrane signaling receptor Proteins 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 238000010396 two-hybrid screening Methods 0.000 description 1
• 238000000108 ultra-filtration Methods 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• 241001430294 unidentified retrovirus Species 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000009278 visceral effect Effects 0.000 description 1
• 235000019166 vitamin D Nutrition 0.000 description 1
• 239000011710 vitamin D Substances 0.000 description 1
• 150000003710 vitamin D derivatives Chemical class 0.000 description 1
• 229940046008 vitamin d Drugs 0.000 description 1
• 108010047303 von Willebrand Factor Proteins 0.000 description 1
• 102100036537 von Willebrand factor Human genes 0.000 description 1
• 229960001134 von willebrand factor Drugs 0.000 description 1
• 230000003313 weakening effect Effects 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1