SK88793A3 - Amylin agonising peptides and their using - Google Patents

Amylin agonising peptides and their using Download PDF

Info

Publication number: SK88793A3
Authority: SK; Slovakia
Prior art keywords: amylin; pro; ser; lys; effective amount
Prior art date: 1991-11-19

Application number

SK887-93A

Other languages

English (en)

Slovak (sk)

Inventor

Laura S L Gaeta

Howard Jones

Elisabeth Albrecht

Original Assignee

Amylin Pharmaceuticals Inc

Priority date (The priority date 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 date listed.)

1991-11-19

Filing date

1992-11-19

Publication date

1994-12-07

1992-11-19 Application filed by Amylin Pharmaceuticals Inc filed Critical Amylin Pharmaceuticals Inc

1994-12-07 Publication of SK88793A3 publication Critical patent/SK88793A3/sk

Links

108010041872 Islet Amyloid Polypeptide Proteins 0.000 title claims abstract description 84
102000036770 Islet Amyloid Polypeptide Human genes 0.000 title claims abstract description 83
108090000765 processed proteins & peptides Proteins 0.000 title description 49
102000004196 processed proteins & peptides Human genes 0.000 title description 7
239000000556 agonist Substances 0.000 claims abstract description 33
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 16
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 claims description 68
102000004877 Insulin Human genes 0.000 claims description 37
108090001061 Insulin Proteins 0.000 claims description 37
238000000034 method Methods 0.000 claims description 36
229940125396 insulin Drugs 0.000 claims description 33
150000001413 amino acids Chemical group 0.000 claims description 30
239000000203 mixture Substances 0.000 claims description 30
102000051325 Glucagon Human genes 0.000 claims description 14
108060003199 Glucagon Proteins 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 14
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 14
229960004666 glucagon Drugs 0.000 claims description 14
230000027455 binding Effects 0.000 claims description 8
230000001225 therapeutic effect Effects 0.000 claims description 8
206010021001 Hypoglycaemic conditions Diseases 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
101000952234 Homo sapiens Sphingolipid delta(4)-desaturase DES1 Proteins 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 4
102100037416 Sphingolipid delta(4)-desaturase DES1 Human genes 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000001769 aryl amino group Chemical group 0.000 claims description 3
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 3
150000008575 L-amino acids Chemical class 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
239000004927 clay Substances 0.000 claims 3
RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 claims 3
208000024891 symptom Diseases 0.000 claims 3
241001514645 Agonis Species 0.000 claims 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
150000002431 hydrogen Chemical class 0.000 claims 2
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 1
125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 claims 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 1
125000004663 dialkyl amino group Chemical group 0.000 claims 1
150000002148 esters Chemical class 0.000 claims 1
150000003951 lactams Chemical class 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 abstract description 4
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 40
150000001875 compounds Chemical class 0.000 description 39
239000011347 resin Substances 0.000 description 37
229920005989 resin Polymers 0.000 description 37
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 33
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 32
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 32
238000004458 analytical method Methods 0.000 description 31
235000001014 amino acid Nutrition 0.000 description 30
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 30
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
238000002360 preparation method Methods 0.000 description 27
239000007788 liquid Substances 0.000 description 24
210000003205 muscle Anatomy 0.000 description 23
125000006239 protecting group Chemical group 0.000 description 21
238000004128 high performance liquid chromatography Methods 0.000 description 20
238000007363 ring formation reaction Methods 0.000 description 19
238000012360 testing method Methods 0.000 description 18
239000000047 product Substances 0.000 description 17
150000003839 salts Chemical class 0.000 description 17
238000010532 solid phase synthesis reaction Methods 0.000 description 17
238000010647 peptide synthesis reaction Methods 0.000 description 16
238000012300 Sequence Analysis Methods 0.000 description 15
238000005251 capillar electrophoresis Methods 0.000 description 15
150000002500 ions Chemical class 0.000 description 15
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 15
230000015572 biosynthetic process Effects 0.000 description 13
235000018417 cysteine Nutrition 0.000 description 13
150000001945 cysteines Chemical class 0.000 description 13
229910052716 thallium Inorganic materials 0.000 description 13
BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 13
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 12
239000002253 acid Substances 0.000 description 12
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 12
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 11
239000007853 buffer solution Substances 0.000 description 11
238000005859 coupling reaction Methods 0.000 description 11
-1 diabetes mellitus Chemical compound 0.000 description 11
239000008103 glucose Substances 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 11
230000000694 effects Effects 0.000 description 10
229920002527 Glycogen Polymers 0.000 description 9
101001081479 Homo sapiens Islet amyloid polypeptide Proteins 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 9
230000008878 coupling Effects 0.000 description 9
238000010168 coupling process Methods 0.000 description 9
229940096919 glycogen Drugs 0.000 description 9
238000001819 mass spectrum Methods 0.000 description 9
229940127438 Amylin Agonists Drugs 0.000 description 8
SHDMMLFAFLZUEV-UHFFFAOYSA-N n-methyl-1,1-diphenylmethanamine Chemical compound C=1C=CC=CC=1C(NC)C1=CC=CC=C1 SHDMMLFAFLZUEV-UHFFFAOYSA-N 0.000 description 8
208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
208000013016 Hypoglycemia Diseases 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
239000008280 blood Substances 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
244000309466 calf Species 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
201000010099 disease Diseases 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
201000001421 hyperglycemia Diseases 0.000 description 6
238000004007 reversed phase HPLC Methods 0.000 description 6
239000000243 solution Substances 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
238000003556 assay Methods 0.000 description 5
239000002585 base Substances 0.000 description 5
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
238000009472 formulation Methods 0.000 description 5
230000002218 hypoglycaemic effect Effects 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
239000003814 drug Substances 0.000 description 4
238000011534 incubation Methods 0.000 description 4
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
239000002953 phosphate buffered saline Substances 0.000 description 4
230000004044 response Effects 0.000 description 4
238000004366 reverse phase liquid chromatography Methods 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
150000003973 alkyl amines Chemical class 0.000 description 3
125000003275 alpha amino acid group Chemical group 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000011260 co-administration Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
230000003345 hyperglycaemic effect Effects 0.000 description 3
239000004026 insulin derivative Substances 0.000 description 3
239000012528 membrane Substances 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
230000002265 prevention Effects 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
AWJGUZSYVIVZGP-YUMQZZPRSA-N Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 AWJGUZSYVIVZGP-YUMQZZPRSA-N 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
101001081470 Rattus norvegicus Islet amyloid polypeptide Proteins 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
230000003941 amyloidogenesis Effects 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
TWXWPPKDQOWNSX-UHFFFAOYSA-N dicyclohexylmethanone Chemical group C1CCCCC1C(=O)C1CCCCC1 TWXWPPKDQOWNSX-UHFFFAOYSA-N 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
230000013632 homeostatic process Effects 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 2
210000004153 islets of langerhan Anatomy 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
229910052751 metal Chemical class 0.000 description 2
239000002184 metal Chemical class 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000003921 oil Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
239000000813 peptide hormone Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
108010053725 prolylvaline Proteins 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
230000005855 radiation Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
238000001308 synthesis method Methods 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
230000006269 (delayed) early viral mRNA transcription Effects 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
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
102000001049 Amyloid Human genes 0.000 description 1
108010094108 Amyloid Proteins 0.000 description 1
208000037259 Amyloid Plaque Diseases 0.000 description 1
102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
102100038521 Calcitonin gene-related peptide 2 Human genes 0.000 description 1
101710117581 Calcitonin gene-related peptide 2 Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000723346 Cinnamomum camphora Species 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-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
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
108010002156 Depsipeptides Proteins 0.000 description 1
101100108820 Drosophila ananassae Amy35 gene Proteins 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
VYUXYMRNGALHEA-DLOVCJGASA-N His-Leu-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O VYUXYMRNGALHEA-DLOVCJGASA-N 0.000 description 1
101000976075 Homo sapiens Insulin Proteins 0.000 description 1
206010020660 Hyperlactacidaemia 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
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
206010022489 Insulin Resistance Diseases 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
229940100389 Sulfonylurea Drugs 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
210000001015 abdomen Anatomy 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
210000001361 achilles tendon Anatomy 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
229910052936 alkali metal sulfate 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
125000003342 alkenyl group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
150000001371 alpha-amino acids Chemical class 0.000 description 1
235000008206 alpha-amino acids Nutrition 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
108091005466 amylin receptors Proteins 0.000 description 1
238000010171 animal model Methods 0.000 description 1
GGAGOQRVJNWXFU-UHFFFAOYSA-N anisole N-methylmethanamine Chemical compound CNC.COC1=CC=CC=C1 GGAGOQRVJNWXFU-UHFFFAOYSA-N 0.000 description 1
OATSTIUYKJBKDX-UHFFFAOYSA-N anisole;methylsulfanylmethane Chemical compound CSC.COC1=CC=CC=C1 OATSTIUYKJBKDX-UHFFFAOYSA-N 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
229960003071 bacitracin Drugs 0.000 description 1
229930184125 bacitracin Natural products 0.000 description 1
CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
229960000846 camphor Drugs 0.000 description 1
229930008380 camphor Natural products 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000007799 cork Substances 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
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 1
230000003247 decreasing effect Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
230000008021 deposition Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
230000006866 deterioration Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
WQZGKKKJIJFFOK-UKLRSMCWSA-N dextrose-2-13c Chemical compound OC[C@H]1OC(O)[13C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-UKLRSMCWSA-N 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000000605 extraction Methods 0.000 description 1
210000003414 extremity Anatomy 0.000 description 1
239000000835 fiber Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical group OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
229940084769 humulin r Drugs 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
229940126904 hypoglycaemic agent Drugs 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000002054 inoculum Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
239000002563 ionic surfactant Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000037323 metabolic rate Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
210000001009 nucleus accumben Anatomy 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
210000002475 olfactory pathway Anatomy 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000035699 permeability Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
150000003147 proline derivatives Chemical class 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
210000004129 prosencephalon Anatomy 0.000 description 1
235000004252 protein component Nutrition 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
230000028327 secretion Effects 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 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
229910001415 sodium ion Inorganic materials 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000001433 sodium tartrate Substances 0.000 description 1
229960002167 sodium tartrate Drugs 0.000 description 1
235000011004 sodium tartrates Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
238000012353 t test Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000008719 thickening Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
210000002303 tibia Anatomy 0.000 description 1
230000014616 translation Effects 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
201000007906 type 1 diabetes mellitus 2 Diseases 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Diabetes (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Endocrinology (AREA)
Obesity (AREA)
Hematology (AREA)
Emergency Medicine (AREA)
Immunology (AREA)
Biochemistry (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Toxicology (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK887-93A 1991-11-19 1992-11-19 Amylin agonising peptides and their using SK88793A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US79426691A	1991-11-19	1991-11-19
PCT/US1992/009842 WO1993010146A1 (en)	1991-11-19	1992-11-19	Amylin agonist peptides and uses therefor

Publications (1)

Publication Number	Publication Date
SK88793A3 true SK88793A3 (en)	1994-12-07

Family

ID=25162163

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK887-93A SK88793A3 (en)	1991-11-19	1992-11-19	Amylin agonising peptides and their using

Country Status (17)

Country	Link
EP (2)	EP0567626B1 (cs)
JP (4)	JP2902115B2 (cs)
AT (1)	ATE205854T1 (cs)
AU (1)	AU714439B2 (cs)
CA (1)	CA2100745C (cs)
CZ (1)	CZ288029B6 (cs)
DE (1)	DE69232064T2 (cs)
DK (1)	DK0567626T3 (cs)
ES (1)	ES2161697T3 (cs)
FI (1)	FI118601B (cs)
GR (1)	GR3036794T3 (cs)
HK (1)	HK1041891A1 (cs)
MD (1)	MD960317A (cs)
NO (2)	NO324405B1 (cs)
RU (1)	RU2130463C1 (cs)
SK (1)	SK88793A3 (cs)
WO (1)	WO1993010146A1 (cs)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU222249B1 (hu)	1991-03-08	2003-05-28	Amylin Pharmaceuticals Inc.	Eljárás amilin agonista peptidszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására
US5625032A (en) *	1993-07-21	1997-04-29	Amylin Pharmaceuticals, Inc.	Selective amylin antagonist peptides and uses therefor
CZ69596A3 (en)	1993-09-07	1997-06-11	Amylin Pharmaceuticals Inc	Application of amylin, amylin agonist, amylin analog agonist or amylin antagonist for preparing a pharmaceutical preparation used for the control of gastrointestinal motility
US6143718A (en) *	1995-06-07	2000-11-07	Amylin Pharmaceuticals, Inc.	Treatment of Type II diabetes mellutis with amylin agonists
US5739106A (en) *	1995-06-07	1998-04-14	Rink; Timothy J.	Appetite regulating compositions
US7312196B2 (en)	1997-01-08	2007-12-25	Amylin Pharmaceuticals, Inc.	Formulations for amylin agonist peptides
US6410511B2 (en)	1997-01-08	2002-06-25	Amylin Pharmaceuticals, Inc.	Formulations for amylin agonist peptides
US7101853B2 (en) *	1997-05-06	2006-09-05	Amylin Pharmaceuticals, Inc.	Method for treating or preventing gastritis using amylin or amylin agonists
US7910548B2 (en)	1997-06-06	2011-03-22	Amylin Pharmaceuticals, Inc.	Methods for treating obesity
EP1044015B1 (en) *	1998-01-09	2008-10-08	Amylin Pharmaceuticals, Inc.	Formulations for amylin agonist peptides with insulin
ATE366259T1 (de) *	1999-03-04	2007-07-15	Praecis Pharm Inc	Beta-amyloid-peptidaggregation regulierende peptide mit d-aminosäuren
GB0002952D0 (en) *	2000-02-09	2000-03-29	Pharma Mar Sa	Process for producing kahalalide F compounds
RU2228174C2 (ru) *	2000-04-10	2004-05-10	Помыткин Игорь Анатольевич	Янтарнокислый бис(2-гидрокси-n,n,n-триметилэтанаминий) для лечения инсулиновой резистентности, сахарного диабета, гиперлипидемии и дислипидемии
GB0128583D0 (en)	2001-11-28	2002-01-23	Rsr Ltd	Detection of autoantibodies indicative of diabetes
WO2004037168A2 (en)	2002-10-18	2004-05-06	Amylin Pharmaceuticals, Inc.	Treatment of pancreatitis with amylin
GB0304367D0 (en) *	2003-02-26	2003-04-02	Pharma Mar Sau	Methods for treating psoriasis
JP2007527365A (ja) *	2003-03-18	2007-09-27	アプライドリサーチシステムズエーアールエスホールディングナームロゼフェンノートシャップ	アミリン凝集阻害剤およびその使用
TW200637872A (en) *	2004-10-26	2006-11-01	Lonza Ag	Thiol group protection and cyclization in solid-phase peptide synthesis
US8394765B2 (en)	2004-11-01	2013-03-12	Amylin Pharmaceuticals Llc	Methods of treating obesity with two different anti-obesity agents
CN101094689B (zh)	2004-11-01	2013-06-12	安米林药品有限责任公司	治疗肥胖以及肥胖相关疾病和病症的方法
CN102343084A (zh)	2005-03-31	2012-02-08	安米林药品公司	用于治疗精神病和精神障碍的胰淀素和胰淀素激动剂
US8168592B2 (en)	2005-10-21	2012-05-01	Amgen Inc.	CGRP peptide antagonists and conjugates
WO2008028914A1 (en)	2006-09-07	2008-03-13	Nycomed Gmbh	Combination treatment for diabetes mellitus
US8309522B2 (en)	2007-02-05	2012-11-13	Amylin Pharmaceuticals, Llc	Neuromedin and FN-38 peptides for treating psychiatric diseases
JP2009149684A (ja) *	2009-03-11	2009-07-09	Amylin Pharmaceut Inc	アミリン作動薬ペプチド用製剤
CA2755068C (en)	2009-03-12	2018-11-06	Keybioscience Ag	Treatment of diabetes and metabolic syndrome
AR097701A1 (es) *	2013-09-19	2016-04-13	Zealand Pharma As	Análogos de amilina
MX2016005995A (es)	2013-11-05	2016-08-17	Ben-Gurion Univ Of The Negev Res And Dev Authority	Compuestos para el tratamiento de diabetes y complicaciones de la enfermedad derivadas de la misma.
CA2947587C (en) *	2014-05-02	2022-10-18	The Research Foundation For The State University Of New York	Islet amyloid polypeptides with improved solubility
BR112017019378A2 (pt) *	2015-03-18	2019-02-19	Zealand Pharma A/S	análogos de amilina
US10071140B2 (en)	2016-09-09	2018-09-11	Zealand Pharma A/S	Amylin analogues
WO2018144671A1 (en)	2017-02-01	2018-08-09	The Research Foundation For The State University Of New York	Mutant islet amyloid polypeptides with improved solubility and methods for using the same
KR102130354B1 (ko) *	2019-08-14	2020-07-06	엘아이지넥스원 주식회사	코어 제거용 이형장치
TWI880227B (zh)	2022-05-30	2025-04-11	丹麥商西蘭製藥公司	澱粉素類似物之液體調配物
IL319599A (en)	2022-09-19	2025-05-01	Zealand Pharma As	Combination therapy
MX2025015167A (es)	2023-06-21	2026-02-03	Zealand Pharma As	Analogos con propiedades mejoradas
TW202504913A (zh)	2023-06-21	2025-02-01	丹麥商西蘭製藥公司	減重
TW202517291A (zh)	2023-06-30	2025-05-01	丹麥商西蘭製藥公司	組合療法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5120712A (en) *	1986-05-05	1992-06-09	The General Hospital Corporation	Insulinotropic hormone
GB8720115D0 (en) *	1987-08-26	1987-09-30	Cooper G J S	Treatment of diabetes mellitus
AU631112B2 (en) *	1988-01-11	1992-11-19	Amylin Corporation	Treatment of type 2 diabetes mellitus
ES2080802T3 (es) *	1989-07-10	1996-02-16	Amylin Pharmaceuticals Inc	Uso de un antagonista de amilina en la preparacion de un medicamento para el tratamiento de la obesidad e hipertension intrinseca y desordenes asociados.
US5234906A (en) *	1991-01-10	1993-08-10	Amylin Pharmaceuticals, Inc.	Hyperglycemic compositions
WO1992015317A1 (en) *	1991-03-08	1992-09-17	Amylin Pharmaceuticals, Inc.	Synthetic preparation of amylin and amylin analogues

1992
- 1992-11-19 CA CA002100745A patent/CA2100745C/en not_active Expired - Lifetime
- 1992-11-19 MD MD96-0317A patent/MD960317A/ro unknown
- 1992-11-19 ES ES92924442T patent/ES2161697T3/es not_active Expired - Lifetime
- 1992-11-19 EP EP92924442A patent/EP0567626B1/en not_active Expired - Lifetime
- 1992-11-19 JP JP5509441A patent/JP2902115B2/ja not_active Expired - Lifetime
- 1992-11-19 SK SK887-93A patent/SK88793A3/sk unknown
- 1992-11-19 DE DE69232064T patent/DE69232064T2/de not_active Expired - Lifetime
- 1992-11-19 RU RU93053497A patent/RU2130463C1/ru active
- 1992-11-19 CZ CZ19931689A patent/CZ288029B6/cs not_active IP Right Cessation
- 1992-11-19 AT AT92924442T patent/ATE205854T1/de active
- 1992-11-19 EP EP01114132A patent/EP1162207A1/en not_active Ceased
- 1992-11-19 WO PCT/US1992/009842 patent/WO1993010146A1/en not_active Ceased
- 1992-11-19 DK DK92924442T patent/DK0567626T3/da active
1993
- 1993-07-16 FI FI933252A patent/FI118601B/fi not_active IP Right Cessation
- 1993-07-19 NO NO19932603A patent/NO324405B1/no not_active IP Right Cessation
1997
- 1997-01-31 AU AU12456/97A patent/AU714439B2/en not_active Expired
1998
- 1998-09-30 JP JP10277573A patent/JPH11152299A/ja not_active Withdrawn
2001
- 2001-10-04 GR GR20010401656T patent/GR3036794T3/el unknown
2002
- 2002-05-02 HK HK02103291.8A patent/HK1041891A1/en unknown
2003
- 2003-01-15 JP JP2003007228A patent/JP2003238594A/ja not_active Withdrawn
2006
- 2006-02-03 JP JP2006027334A patent/JP4018116B2/ja not_active Expired - Lifetime
2007
- 2007-06-25 NO NO20073265A patent/NO20073265L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
AU1245697A (en)	1997-03-27
MD960317A (ro)	1998-05-31
WO1993010146A1 (en)	1993-05-27
NO932603D0 (no)	1993-07-19
DE69232064T2 (de)	2002-03-28
CA2100745C (en)	2007-07-31
AU3075392A (en)	1993-06-15
NO324405B1 (no)	2007-10-08
EP0567626A1 (en)	1993-11-03
AU714439B2 (en)	2000-01-06
HK1041891A1 (en)	2002-07-26
JPH06504794A (ja)	1994-06-02
GR3036794T3 (en)	2002-01-31
CA2100745A1 (en)	1993-05-20
CZ288029B6 (cs)	2001-04-11
NO20073265L (no)	1993-09-17
FI933252A0 (fi)	1993-07-16
JP2006213716A (ja)	2006-08-17
EP1162207A1 (en)	2001-12-12
ATE205854T1 (de)	2001-10-15
RU2130463C1 (ru)	1999-05-20
JP4018116B2 (ja)	2007-12-05
AU673147B2 (en)	1996-10-31
EP0567626B1 (en)	2001-09-19
JPH11152299A (ja)	1999-06-08
FI933252L (fi)	1993-08-23
JP2902115B2 (ja)	1999-06-07
DE69232064D1 (de)	2001-10-25
DK0567626T3 (da)	2001-12-17
ES2161697T3 (es)	2001-12-16
NO932603L (no)	1993-09-17
FI118601B (fi)	2008-01-15
JP2003238594A (ja)	2003-08-27
CZ168993A3 (en)	1994-04-13

Publication	Publication Date	Title
SK88793A3 (en)	1994-12-07	Amylin agonising peptides and their using
US7271238B2 (en)	2007-09-18	Amylin agonist peptides and uses therefor
AU2017216533B2 (en)	2019-10-03	Improved peptide pharmaceuticals
AU766545B2 (en)	2003-10-16	Novel anti-diabetic peptides
JP2022172128A (ja)	2022-11-15	インスリン抵抗性のための改善されたペプチド医薬品
JP2003501361A (ja)	2003-01-14	妊娠糖尿病の治療のためのエキセンジンおよびそのアゴニストの使用
JP2001513512A (ja)	2001-09-04	新規なエキセンディン作動剤化合物
JP2003522721A (ja)	2003-07-29	新規なエキセンジンアゴニスト化合物
SK88893A3 (en)	1994-03-09	Novel amylin antagonist peptides and uses therefor
EA038073B1 (ru)	2021-07-01	Ацилированное инсулиновое соединение
JP2002522355A (ja)	2002-07-23	新規な混合アミリン活性化合物
AU669636B2 (en)	1996-06-13	Amylin antagonists and agonists
KR20230106481A (ko)	2023-07-13	지속형 지방산-펩타이드 유도체 및 이의 용도
US20040127412A1 (en)	2004-07-01	Modified GLP-1 peptides with increased biological potency
AU673147C (en)	1998-04-23	Amylin agonist peptides and uses therefor
HK1038025B (en)	2007-04-27	Novel anti-diabetic peptides