MXPA04006679A - Analogos extendidos de peptido-1 de tipo glucagon. - Google Patents
Analogos extendidos de peptido-1 de tipo glucagon.Info
- Publication number
- MXPA04006679A MXPA04006679A MXPA04006679A MXPA04006679A MXPA04006679A MX PA04006679 A MXPA04006679 A MX PA04006679A MX PA04006679 A MXPA04006679 A MX PA04006679A MX PA04006679 A MXPA04006679 A MX PA04006679A MX PA04006679 A MXPA04006679 A MX PA04006679A
- Authority
- MX
- Mexico
- Prior art keywords
- gly
- glp
- ser
- lys
- ala
- Prior art date
Links
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 title claims description 61
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 claims abstract 46
- 150000001413 amino acids Chemical group 0.000 claims description 103
- 229940024606 amino acid Drugs 0.000 claims description 92
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 75
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 50
- 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 34
- 238000006467 substitution reaction Methods 0.000 claims description 34
- 229960002885 histidine Drugs 0.000 claims description 29
- -1 GLP-1 compound Chemical class 0.000 claims description 18
- 102000004877 Insulin Human genes 0.000 claims description 17
- 108090001061 Insulin Proteins 0.000 claims description 17
- 229940125396 insulin Drugs 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 14
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 claims description 13
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 claims description 11
- MSECZMWQBBVGEN-LURJTMIESA-N (2s)-2-azaniumyl-4-(1h-imidazol-5-yl)butanoate Chemical compound OC(=O)[C@@H](N)CCC1=CN=CN1 MSECZMWQBBVGEN-LURJTMIESA-N 0.000 claims description 10
- UYEGXSNFZXWSDV-BYPYZUCNSA-N (2s)-3-(2-amino-1h-imidazol-5-yl)-2-azaniumylpropanoate Chemical compound OC(=O)[C@@H](N)CC1=CNC(N)=N1 UYEGXSNFZXWSDV-BYPYZUCNSA-N 0.000 claims description 10
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims description 10
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 claims description 10
- 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 claims description 10
- ZCKYOWGFRHAZIQ-UHFFFAOYSA-N dihydrourocanic acid Chemical compound OC(=O)CCC1=CNC=N1 ZCKYOWGFRHAZIQ-UHFFFAOYSA-N 0.000 claims description 10
- KQMBIBBJWXGSEI-ROLXFIACSA-N (2s)-2-amino-3-hydroxy-3-(1h-imidazol-5-yl)propanoic acid Chemical compound OC(=O)[C@@H](N)C(O)C1=CNC=N1 KQMBIBBJWXGSEI-ROLXFIACSA-N 0.000 claims description 9
- 229930195721 D-histidine Natural products 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 239000008103 glucose Substances 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 8
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims description 8
- AJFGLTPLWPTALJ-SSDOTTSWSA-N (2s)-2-azaniumyl-2-(fluoromethyl)-3-(1h-imidazol-5-yl)propanoate Chemical compound FC[C@@](N)(C(O)=O)CC1=CN=CN1 AJFGLTPLWPTALJ-SSDOTTSWSA-N 0.000 claims description 7
- MGOGKPMIZGEGOZ-REOHCLBHSA-N (2s)-2-amino-3-hydroxypropanamide Chemical compound OC[C@H](N)C(N)=O MGOGKPMIZGEGOZ-REOHCLBHSA-N 0.000 claims description 6
- 230000001419 dependent effect Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 201000001421 hyperglycemia Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- HRRYYCWYCMJNGA-ZETCQYMHSA-N alpha-methyl-L-histidine Chemical compound OC(=O)[C@](N)(C)CC1=CN=CN1 HRRYYCWYCMJNGA-ZETCQYMHSA-N 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- ULEBESPCVWBNIF-BYPYZUCNSA-N L-arginine amide Chemical compound NC(=O)[C@@H](N)CCCNC(N)=N ULEBESPCVWBNIF-BYPYZUCNSA-N 0.000 claims description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 44
- RMLTYXMJJRBQTB-RZKHNPSRSA-N (2s)-2-amino-4-fluoro-3-(1h-imidazol-5-yl)butanoic acid Chemical compound OC(=O)[C@@H](N)C(CF)C1=CNC=N1 RMLTYXMJJRBQTB-RZKHNPSRSA-N 0.000 claims 1
- 125000002437 D-histidyl group Chemical group N[C@@H](C(=O)*)CC=1N=CNC1 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000010606 normalization Methods 0.000 claims 1
- 238000012986 modification Methods 0.000 abstract description 3
- 230000004048 modification Effects 0.000 abstract description 3
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 100
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 81
- 235000001014 amino acid Nutrition 0.000 description 81
- 102100040918 Pro-glucagon Human genes 0.000 description 73
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 62
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 62
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 53
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 53
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 40
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 40
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 31
- 239000004471 Glycine Chemical group 0.000 description 23
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 22
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 21
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 21
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical group CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 21
- 239000004474 valine Substances 0.000 description 21
- 102000004196 processed proteins & peptides Human genes 0.000 description 19
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 18
- YONJPLIBVIENNO-LAEOZQHASA-N (2s)-2-amino-5-[[(2r)-3-[(1s)-1-amino-1-carboxy-2-methylpropan-2-yl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound OC(=O)[C@H](N)C(C)(C)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YONJPLIBVIENNO-LAEOZQHASA-N 0.000 description 17
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 17
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 17
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Chemical group CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 17
- 229960000310 isoleucine Drugs 0.000 description 17
- 108700034543 penicillamine-glutathione mixed disulfide Proteins 0.000 description 17
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 16
- 239000004472 Lysine Substances 0.000 description 15
- 235000018977 lysine Nutrition 0.000 description 15
- DSEKYWAQQVUQTP-UHFFFAOYSA-N Cerin Chemical group CC12CCC3(C)C4CC(C)(C)CCC4(C)CCC3(C)C2CCC2(C)C1CC(O)C(=O)C2C DSEKYWAQQVUQTP-UHFFFAOYSA-N 0.000 description 14
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical group CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 14
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 235000013930 proline Nutrition 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical group CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 12
- 235000013922 glutamic acid Nutrition 0.000 description 11
- 239000004220 glutamic acid Substances 0.000 description 11
- 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 10
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical group CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 10
- 239000004473 Threonine Chemical group 0.000 description 10
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 10
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 9
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 9
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 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 9
- 229930182817 methionine Chemical group 0.000 description 9
- 239000004475 Arginine Substances 0.000 description 8
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 8
- 235000009697 arginine Nutrition 0.000 description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 8
- 235000014304 histidine Nutrition 0.000 description 8
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 8
- 230000003389 potentiating effect Effects 0.000 description 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 6
- 235000004279 alanine Nutrition 0.000 description 6
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- 108090000204 Dipeptidase 1 Proteins 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 102000006635 beta-lactamase Human genes 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000002473 insulinotropic effect Effects 0.000 description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical group OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 235000003704 aspartic acid Nutrition 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 3
- 230000003345 hyperglycaemic effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000003914 insulin secretion Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 2
- 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 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
- 102100041030 Pancreas/duodenum homeobox protein 1 Human genes 0.000 description 2
- 101710144033 Pancreas/duodenum homeobox protein 1 Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108091027981 Response element Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000005441 aurora Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 229960004666 glucagon Drugs 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000000517 particles from gas-saturated solution Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
- CFYIUBWVKZQDOG-UHFFFAOYSA-N 4-[[2-[[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-4-oxobutanoic acid Chemical compound C=1C=C([N+]([O-])=O)C=CC=1NC(=O)C(NC(=O)CNC(=O)CNC(=O)CCC(=O)O)CC1=CC=CC=C1 CFYIUBWVKZQDOG-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101000883510 Bos taurus Chitinase-3-like protein 1 Proteins 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000700198 Cavia 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
- 108020004414 DNA Proteins 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 101000804902 Drosophila melanogaster Xaa-Pro aminopeptidase ApepP Proteins 0.000 description 1
- 241001379910 Ephemera danica Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001021281 Homo sapiens Protein HEXIM1 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 101710092928 Insulin-like peptide-1 Proteins 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
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101000993459 Mus musculus Metal transporter CNNM1 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102100036307 Protein HEXIM1 Human genes 0.000 description 1
- 101100321409 Rattus norvegicus Zdhhc23 gene Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Chemical group OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 108010027597 alpha-chymotrypsin Proteins 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000006242 amine protecting group Chemical group 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000003111 delayed effect 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
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000004955 epithelial membrane Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- UKVFVQPAANCXIL-FJVFSOETSA-N glp-1 (1-37) amide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 UKVFVQPAANCXIL-FJVFSOETSA-N 0.000 description 1
- 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 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000010454 slate Substances 0.000 description 1
- 239000008149 soap solution Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water 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
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 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
- C07K14/605—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Zoology (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34647402P | 2002-01-08 | 2002-01-08 | |
| US40509702P | 2002-08-21 | 2002-08-21 | |
| PCT/US2003/000001 WO2003058203A2 (en) | 2002-01-08 | 2003-01-03 | Extended glucagon-like peptide-1 analogs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA04006679A true MXPA04006679A (es) | 2004-11-10 |
Family
ID=26994870
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA04006679A MXPA04006679A (es) | 2002-01-08 | 2003-01-03 | Analogos extendidos de peptido-1 de tipo glucagon. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US7482321B2 (enExample) |
| EP (1) | EP1585959A4 (enExample) |
| JP (1) | JP4282485B2 (enExample) |
| AR (1) | AR038102A1 (enExample) |
| AU (1) | AU2003200839B2 (enExample) |
| BR (1) | BR0306706A (enExample) |
| CA (1) | CA2468700A1 (enExample) |
| MX (1) | MXPA04006679A (enExample) |
| PE (1) | PE20030820A1 (enExample) |
| TW (1) | TW200306202A (enExample) |
| WO (1) | WO2003058203A2 (enExample) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0407936A (pt) | 2003-03-19 | 2006-02-21 | Lilly Co Eli | composto de glp-1 peguilado, método de estimular o receptor de glp-1 em um indivìduo, e, uso de composto glp-1 peguilado |
| WO2005056036A2 (en) | 2003-12-09 | 2005-06-23 | Novo Nordisk A/S | Regulation of food preference using glp-1 agonists |
| US7538185B2 (en) | 2004-01-08 | 2009-05-26 | Theratechnologies Inc. | Glucagon-like peptide-1 analogs with long duration of action |
| US8410047B2 (en) | 2004-06-11 | 2013-04-02 | Novo Nordisk A/S | Counteracting drug-induced obesity using GLP-1 agonists |
| CA2576755A1 (en) * | 2004-08-18 | 2006-03-02 | Eli Lilly And Company | Selective vpac2 receptor peptide agonists |
| ES2541633T3 (es) | 2005-01-14 | 2015-07-22 | Wuxi Grandchamp Pharmaceutical Technology Co., Ltd. | Exendinas modificadas y usos de las mismas |
| TWI372629B (en) | 2005-03-18 | 2012-09-21 | Novo Nordisk As | Acylated glp-1 compounds |
| MX2007011307A (es) | 2005-03-18 | 2007-10-08 | Novo Nordisk As | Compuestos de glp-1 extendidos. |
| KR20080021636A (ko) * | 2005-05-05 | 2008-03-07 | 카딜라 핼쓰캐어 리미티드 | Ｇｌｐ-1 아고니스트인 신규 화합물 |
| EA012442B1 (ru) * | 2005-05-13 | 2009-10-30 | Эли Лилли Энд Компани | Пегилированные соединения glp-1 |
| EP1915393A1 (en) * | 2005-08-11 | 2008-04-30 | Eli Lilly And Company | Selective vpac2 receptor peptide agonists |
| ES2397289T3 (es) * | 2005-09-22 | 2013-03-06 | Biocompatibles Uk Ltd. | Polipéptidos de fusión de GLP-1 (péptido 1 de tipo glucagón) con resistencia a peptidasa incrementada |
| BRPI0617740A2 (pt) | 2005-10-26 | 2011-08-02 | Lilly Co Eli | agonistas seletivos peptìdicos do receptor vpac2, composição farmacêutica e uso dos referidos agonistas |
| JP2009514900A (ja) * | 2005-11-04 | 2009-04-09 | スミスクライン・ビーチャム・コーポレイション | 血糖降下剤の投与方法 |
| WO2007056362A2 (en) | 2005-11-07 | 2007-05-18 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| EP2364735A3 (en) | 2005-12-16 | 2012-04-11 | Nektar Therapeutics | Branched PEG conjugates of GLP-1 |
| BRPI0708341A2 (pt) * | 2006-02-28 | 2011-05-24 | Lilly Co Eli | agonistas peptìdicos seletivos do receptor vpac2 |
| WO2007113205A1 (en) * | 2006-04-03 | 2007-10-11 | Novo Nordisk A/S | Glp-1 peptide agonists |
| AU2007240313B2 (en) | 2006-04-20 | 2012-02-02 | Amgen Inc. | GLP-1 compounds |
| EP1854455B1 (en) | 2006-05-10 | 2009-10-07 | Biocompatibles UK Limited | Spherical microcapsules comprising GLP-1 peptides, their production and use |
| JO2945B1 (en) | 2006-09-13 | 2016-03-15 | سميث كلاين بيتشام كوربوريشن | Methods of giving prolonged hypoglycemic agents |
| EA017849B1 (ru) | 2007-02-15 | 2013-03-29 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Соагонисты глюкагоновых/glp-1-рецепторов |
| EP1972349A1 (en) * | 2007-03-21 | 2008-09-24 | Biocompatibles UK Limited | GLP-1 fusion peptides conjugated to polymer(s), their production and use |
| EP1975176A1 (en) * | 2007-03-27 | 2008-10-01 | Biocompatibles UK Limited | Novel glp-1 fusion peptides, their production and use |
| EP2185178B1 (en) * | 2007-08-03 | 2017-08-23 | Eli Lilly And Company | Use of an fgf-21 compound and a glp-1 compound for the treatment of obesity |
| WO2009058734A1 (en) | 2007-10-30 | 2009-05-07 | Indiana University Research And Technology Corporation | Compounds exhibiting glucagon antagonist and glp-1 agonist activity |
| EA020326B9 (ru) | 2008-06-17 | 2015-03-31 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Агонисты смешанного действия на основе глюкозозависимого инсулинотропного пептида для лечения нарушений обмена веществ и ожирения |
| US8450270B2 (en) * | 2008-06-17 | 2013-05-28 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability in physiological pH buffers |
| WO2010054326A2 (en) | 2008-11-07 | 2010-05-14 | The General Hospital Corporation | C-terminal fragments of glucagon-like peptide-1 (glp-1) |
| SMT201700189T1 (it) | 2008-12-10 | 2017-05-08 | Glaxosmithkline Llc | Composizioni farmaceutiche di albiglutide |
| CN102325539A (zh) | 2008-12-19 | 2012-01-18 | 印第安纳大学研究及科技有限公司 | 基于酰胺的胰高血糖素超家族肽前药 |
| CN102459325B (zh) | 2009-06-16 | 2015-03-25 | 印第安纳大学科技研究有限公司 | 胃抑胜肽受体活化的胰高血糖素化合物 |
| EP2528618A4 (en) | 2010-01-27 | 2015-05-27 | Univ Indiana Res & Tech Corp | GLUCAGON ANTAGONISTE AND GIP AGONISTS CONJUGATES AND COMPOSITIONS FOR THE TREATMENT OF METABOLISM DISEASES AND ADIPOSITAS |
| WO2011140176A1 (en) | 2010-05-04 | 2011-11-10 | Glaxosmithkline Llc | Methods for treating or preventing cardiovascular disorders and providing cardiovascular protection |
| CN103179976A (zh) | 2010-05-13 | 2013-06-26 | 印第安纳大学研究及科技有限公司 | 呈现g蛋白偶联受体活性的胰高血糖素超家族肽 |
| EP2569000B1 (en) | 2010-05-13 | 2017-09-27 | Indiana University Research and Technology Corporation | Glucagon superfamily peptides exhibiting nuclear hormone receptor activity |
| RU2580317C2 (ru) | 2010-06-24 | 2016-04-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов |
| WO2012054822A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Pharmacologically active polymer-glp-1 conjugates |
| WO2012054861A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Glp-1 polymer conjugates having a releasable linkage |
| US9040481B2 (en) | 2010-11-02 | 2015-05-26 | The General Hospital Corporation | Methods for treating steatotic disease |
| MX347014B (es) | 2010-11-24 | 2017-04-07 | Durect Corp | Composición para administración de fármaco biodegradable. |
| BR112013015389A2 (pt) | 2010-12-22 | 2016-11-22 | Univ Indiana Res & Tech Corp | análogo de glucagon exibindo atividade de receptor gip |
| CA2839867A1 (en) | 2011-06-22 | 2012-12-27 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| PE20140724A1 (es) | 2011-06-22 | 2014-07-10 | Univ Indiana Res & Tech Corp | Coagonistas del receptor de glucagon/glp-1 |
| EP2729157B1 (en) | 2011-07-06 | 2019-01-16 | The General Hospital Corporation | A pentapeptide derived from the c-terminus of glucagon-like peptide 1 (glp-1) for use in treatment |
| CN102363633B (zh) * | 2011-11-16 | 2013-11-20 | 天津拓飞生物科技有限公司 | 胰高血糖素样肽-1突变体多肽及其制备方法、药物组合物和其应用 |
| US8859491B2 (en) | 2011-11-17 | 2014-10-14 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting glucocorticoid receptor activity |
| EP2782590A4 (en) | 2011-11-23 | 2016-08-03 | Durect Corp | BIODEGRADABLE AND MEDIUM-RADIATED STERILIZED MEDICAMENTAL COMPOSITIONS |
| JP6311708B2 (ja) | 2012-06-21 | 2018-04-18 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | Ｇｉｐ受容体活性を示すグルカゴンアナローグ |
| KR20160021183A (ko) * | 2013-06-20 | 2016-02-24 | 노보 노르디스크 에이/에스 | Glp-1 유도체 및 그것의 용도 |
| US10626156B2 (en) | 2013-12-06 | 2020-04-21 | Jie Han | Bioreversable promoieties for nitrogen-containing and hydroxyl-containing drugs |
| CN105764491A (zh) | 2013-12-09 | 2016-07-13 | 度瑞公司 | 药物活性剂复合物、聚合物复合物，以及包括其的组合物和方法 |
| CN106999602B (zh) | 2014-11-27 | 2022-02-01 | 诺和诺德股份有限公司 | Glp-1衍生物及其用途 |
| JP6691125B2 (ja) | 2014-12-17 | 2020-04-28 | ノヴォ ノルディスク アー／エス | Ｇｌｐ−１誘導体及びその使用 |
| PE20211417A1 (es) | 2018-04-05 | 2021-08-02 | Sun Pharmaceutical Ind Ltd | Analogos novedosos de glp-1 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2283025T3 (es) * | 1996-08-30 | 2007-10-16 | Novo Nordisk A/S | Derivados de glp-1.1. |
| ATE466027T1 (de) * | 1998-02-27 | 2010-05-15 | Novo Nordisk As | Abkömmlinge von glp-1 analogen |
| DE69942307D1 (de) | 1998-02-27 | 2010-06-10 | Novo Nordisk As | N-terminal veränderte glp-1 abkömmlinge |
| JP2002523333A (ja) | 1998-07-31 | 2002-07-30 | ノボ ノルディスク アクティーゼルスカブ | Ｉｉ型糖尿病を予防するためのｇｌｐ−１及び類似体の利用 |
| DK1355942T3 (da) * | 2000-12-07 | 2008-11-17 | Lilly Co Eli | GLP-1-fusionsproteiner |
| ATE408414T1 (de) | 2001-07-31 | 2008-10-15 | Us Gov Health & Human Serv | Glp 1 exendin 4 peptidanaloga und deren verwendungen |
| CN1635900A (zh) * | 2001-08-28 | 2005-07-06 | 伊莱利利公司 | Glp－1和基础胰岛素的预混合物 |
| US7179788B2 (en) * | 2001-10-19 | 2007-02-20 | Eli Lilly And Company | Biphasic mixtures of GLP-1 and insulin |
-
2003
- 2003-01-03 BR BRPI0306706-8A patent/BR0306706A/pt not_active IP Right Cessation
- 2003-01-03 MX MXPA04006679A patent/MXPA04006679A/es unknown
- 2003-01-03 JP JP2003558463A patent/JP4282485B2/ja not_active Expired - Fee Related
- 2003-01-03 TW TW092100093A patent/TW200306202A/zh unknown
- 2003-01-03 AR ARP030100014A patent/AR038102A1/es unknown
- 2003-01-03 AU AU2003200839A patent/AU2003200839B2/en not_active Ceased
- 2003-01-03 WO PCT/US2003/000001 patent/WO2003058203A2/en not_active Ceased
- 2003-01-03 US US10/499,111 patent/US7482321B2/en not_active Expired - Fee Related
- 2003-01-03 EP EP03700026A patent/EP1585959A4/en not_active Withdrawn
- 2003-01-03 CA CA002468700A patent/CA2468700A1/en not_active Abandoned
- 2003-01-06 PE PE2003000021A patent/PE20030820A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1585959A2 (en) | 2005-10-19 |
| AR038102A1 (es) | 2004-12-29 |
| US7482321B2 (en) | 2009-01-27 |
| US20060014241A1 (en) | 2006-01-19 |
| WO2003058203A2 (en) | 2003-07-17 |
| WO2003058203A3 (en) | 2007-02-01 |
| CA2468700A1 (en) | 2003-07-17 |
| AU2003200839B2 (en) | 2008-12-11 |
| JP2005528337A (ja) | 2005-09-22 |
| BR0306706A (pt) | 2007-03-27 |
| AU2003200839A1 (en) | 2003-07-24 |
| EP1585959A4 (en) | 2007-11-14 |
| JP4282485B2 (ja) | 2009-06-24 |
| TW200306202A (en) | 2003-11-16 |
| PE20030820A1 (es) | 2003-10-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7482321B2 (en) | Extended glucagon-like peptide-1 analogs | |
| AU2003200839A2 (en) | Extended glucagon-like peptide-1 analogs | |
| KR100593348B1 (ko) | 글루카곤-유사 펩티드-1 유사체 | |
| CN102197049B (zh) | 胰岛淀粉样多肽衍生物 | |
| KR102544419B1 (ko) | 글루카곤 및 glp-1 공-효능제 화합물 | |
| EP1294757B1 (en) | Glucagon-like peptide-1 analogs | |
| US9920106B2 (en) | GLP-1 compounds | |
| US20060252916A1 (en) | Modified glucagon-like peptide-1 analogs | |
| US20090062192A1 (en) | Dimeric Peptide Agonists of the Glp-1 Receptor | |
| NO328077B1 (no) | Anvendelse av en eksendin eller eksendinagonist for fremstilling av en farmasoytisk formulering. | |
| ZA200502571B (en) | Stabilized exendin-4-compounds. | |
| US7608587B2 (en) | Exendin 4 polypeptide fragment | |
| KR20120116942A (ko) | 폴리펩티드 접합체 | |
| WO2024213022A1 (zh) | 肠促胰素类似物及其制备方法和应用 | |
| US20110269680A1 (en) | Glp-1 analogs and uses thereof | |
| CN117603364A (zh) | 一类GLP-1/glucagon/Y2受体三重激动剂及其应用 | |
| HK1207088B (zh) | N-末端氨基酸经修饰的促胰岛素释放肽衍生物 | |
| HK1055121B (en) | Glucagon-like peptide-1 analogs |