MX2012007449A - Analogo peptidico de oxintomodulina. - Google Patents
Analogo peptidico de oxintomodulina.Info
- Publication number
- MX2012007449A MX2012007449A MX2012007449A MX2012007449A MX2012007449A MX 2012007449 A MX2012007449 A MX 2012007449A MX 2012007449 A MX2012007449 A MX 2012007449A MX 2012007449 A MX2012007449 A MX 2012007449A MX 2012007449 A MX2012007449 A MX 2012007449A
- Authority
- MX
- Mexico
- Prior art keywords
- cys
- oxintomodulin
- peptide analogue
- asn
- ala
- Prior art date
Links
- 101800001388 Oxyntomodulin Proteins 0.000 title claims abstract 5
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 19
- 208000008589 Obesity Diseases 0.000 claims abstract description 16
- 235000020824 obesity Nutrition 0.000 claims abstract description 16
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 166
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 12
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 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 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims 2
- KRBMQYPTDYSENE-BQBZGAKWSA-N His-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CNC=N1 KRBMQYPTDYSENE-BQBZGAKWSA-N 0.000 claims 1
- 108010018006 histidylserine Proteins 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 54
- 239000008103 glucose Substances 0.000 description 50
- 241000699670 Mus sp. Species 0.000 description 33
- 210000004027 cell Anatomy 0.000 description 32
- 210000004369 blood Anatomy 0.000 description 29
- 239000008280 blood Substances 0.000 description 29
- 229920001223 polyethylene glycol Polymers 0.000 description 29
- 239000003981 vehicle Substances 0.000 description 27
- 230000000694 effects Effects 0.000 description 26
- 239000002202 Polyethylene glycol Substances 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 20
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 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(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 description 20
- 102100040918 Pro-glucagon Human genes 0.000 description 20
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 18
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical group 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 17
- 229960004666 glucagon Drugs 0.000 description 17
- 102000051325 Glucagon Human genes 0.000 description 16
- 108060003199 Glucagon Proteins 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 230000037396 body weight Effects 0.000 description 16
- 235000013305 food Nutrition 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 108010063919 Glucagon Receptors Proteins 0.000 description 14
- 102100040890 Glucagon receptor Human genes 0.000 description 14
- 210000002381 plasma Anatomy 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 12
- 238000007912 intraperitoneal administration Methods 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 11
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 11
- 101001040075 Homo sapiens Glucagon receptor Proteins 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 238000007446 glucose tolerance test Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000006228 supernatant Substances 0.000 description 10
- 230000004580 weight loss Effects 0.000 description 10
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- 102000004877 Insulin Human genes 0.000 description 9
- 108090001061 Insulin Proteins 0.000 description 9
- 229940098773 bovine serum albumin Drugs 0.000 description 9
- 229940125396 insulin Drugs 0.000 description 9
- 239000008188 pellet Substances 0.000 description 9
- 230000036515 potency Effects 0.000 description 9
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000013641 positive control Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000001061 Dunnett's test Methods 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 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 7
- 230000002473 insulinotropic effect Effects 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 6
- 239000000370 acceptor Substances 0.000 description 6
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000008030 elimination Effects 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 102000056448 human GLP1R Human genes 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 238000007410 oral glucose tolerance test Methods 0.000 description 6
- 230000006320 pegylation Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 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 5
- 239000007995 HEPES buffer Substances 0.000 description 5
- 101500028776 Homo sapiens Oxyntomodulin Proteins 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 4
- 206010056997 Impaired fasting glucose Diseases 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 239000012148 binding buffer Substances 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 229910001629 magnesium chloride Inorganic materials 0.000 description 4
- GNZCSGYHILBXLL-UHFFFAOYSA-N n-tert-butyl-6,7-dichloro-3-methylsulfonylquinoxalin-2-amine Chemical compound ClC1=C(Cl)C=C2N=C(S(C)(=O)=O)C(NC(C)(C)C)=NC2=C1 GNZCSGYHILBXLL-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 238000002821 scintillation proximity assay Methods 0.000 description 4
- 239000007929 subcutaneous injection Substances 0.000 description 4
- 238000010254 subcutaneous injection Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 208000002705 Glucose Intolerance Diseases 0.000 description 3
- 240000000786 Margyricarpus pinnatus Species 0.000 description 3
- 235000010838 Margyricarpus pinnatus Nutrition 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010033307 Overweight Diseases 0.000 description 3
- 241001662443 Phemeranthus parviflorus Species 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 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 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 238000002825 functional assay Methods 0.000 description 3
- 238000011990 functional testing Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 201000009104 prediabetes syndrome Diseases 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000001525 receptor binding assay Methods 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 229930195711 D-Serine Natural products 0.000 description 2
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
- 108010011459 Exenatide Proteins 0.000 description 2
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 2
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 2
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108010019598 Liraglutide Proteins 0.000 description 2
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)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](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)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=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- LTYOQGRJFJAKNA-KKIMTKSISA-N Malonyl CoA Natural products S(C(=O)CC(=O)O)CCNC(=O)CCNC(=O)[C@@H](O)C(CO[P@](=O)(O[P@](=O)(OC[C@H]1[C@@H](OP(=O)(O)O)[C@@H](O)[C@@H](n2c3ncnc(N)c3nc2)O1)O)O)(C)C LTYOQGRJFJAKNA-KKIMTKSISA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 235000004347 Perilla Nutrition 0.000 description 2
- 244000124853 Perilla frutescens Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 238000012440 amplified luminescent proximity homogeneous assay Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000002785 anti-thrombosis Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004061 bleaching Methods 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229960001519 exenatide Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 208000004104 gestational diabetes Diseases 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 230000009716 hepatic expression Effects 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229940057428 lactoperoxidase Drugs 0.000 description 2
- 229960002701 liraglutide Drugs 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- LTYOQGRJFJAKNA-DVVLENMVSA-N malonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-DVVLENMVSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 102000014187 peptide receptors Human genes 0.000 description 2
- 108010011903 peptide receptors Proteins 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000004114 suspension culture Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 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
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- DYWUPCCKOVTCFZ-LBPRGKRZSA-N (2s)-2-amino-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoic acid Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=C(C[C@H](N)C(O)=O)C2=C1 DYWUPCCKOVTCFZ-LBPRGKRZSA-N 0.000 description 1
- GVIXTVCDNCXXSH-AWEZNQCLSA-N (2s)-2-amino-5-[[amino-[(2,2,4,6,7-pentamethyl-3h-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCN=C(N)NS(=O)(=O)C1=C(C)C(C)=C2OC(C)(C)CC2=C1C GVIXTVCDNCXXSH-AWEZNQCLSA-N 0.000 description 1
- VVQIIIAZJXTLRE-QMMMGPOBSA-N (2s)-2-amino-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC[C@H](N)C(O)=O VVQIIIAZJXTLRE-QMMMGPOBSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 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
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- 125000001431 2-aminoisobutyric acid group Chemical group [#6]C([#6])(N*)C(*)=O 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 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
- 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
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 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
- 125000000734 D-serino group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha 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
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 101150094724 PCSK9 gene Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 108010058003 Proglucagon Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 241000700159 Rattus Species 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
- 102400000827 Saposin-D Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 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
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 101150115889 al gene Proteins 0.000 description 1
- 125000000217 alkyl 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
- FUOOLUPWFVMBKG-UHFFFAOYSA-N alpha-amino-isobutyric acid Natural products CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000037058 blood plasma level Effects 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
- 150000001768 cations Chemical class 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 108091005606 gamma-carboxylated proteins Proteins 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 229940100689 human protein c Drugs 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 208000011661 metabolic syndrome X Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 235000006286 nutrient intake Nutrition 0.000 description 1
- 238000013116 obese mouse model Methods 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 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 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- CLKZWXHKFXZIMA-UHFFFAOYSA-N pyrinuron Chemical group C1=CC([N+](=O)[O-])=CC=C1NC(=O)NCC1=CC=CN=C1 CLKZWXHKFXZIMA-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 231100000272 reduced body weight Toxicity 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- 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
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28888409P | 2009-12-22 | 2009-12-22 | |
| US35256910P | 2010-06-08 | 2010-06-08 | |
| PCT/US2010/060380 WO2011087671A1 (en) | 2009-12-22 | 2010-12-15 | Oxyntomodulin peptide analogue |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2012007449A true MX2012007449A (es) | 2012-11-23 |
Family
ID=43568014
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2012007449A MX2012007449A (es) | 2009-12-22 | 2010-12-15 | Analogo peptidico de oxintomodulina. |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US8415296B2 (https=) |
| EP (1) | EP2515927B1 (https=) |
| JP (1) | JP5717758B2 (https=) |
| KR (1) | KR101399692B1 (https=) |
| CN (1) | CN102665752B (https=) |
| AR (1) | AR079344A1 (https=) |
| AU (1) | AU2010341650B2 (https=) |
| BR (1) | BR112012017054A2 (https=) |
| CA (1) | CA2784668C (https=) |
| CL (1) | CL2012001685A1 (https=) |
| CO (1) | CO6551737A2 (https=) |
| CR (1) | CR20120339A (https=) |
| DO (1) | DOP2012000175A (https=) |
| EA (1) | EA201290557A1 (https=) |
| EC (1) | ECSP12011988A (https=) |
| ES (1) | ES2512141T3 (https=) |
| GT (1) | GT201200205A (https=) |
| MA (1) | MA33826B1 (https=) |
| MX (1) | MX2012007449A (https=) |
| NZ (1) | NZ600732A (https=) |
| PE (1) | PE20121721A1 (https=) |
| SG (1) | SG181872A1 (https=) |
| TN (1) | TN2012000303A1 (https=) |
| TW (1) | TWI451873B (https=) |
| UA (1) | UA106399C2 (https=) |
| WO (1) | WO2011087671A1 (https=) |
Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| CA2913805A1 (en) | 2005-11-07 | 2007-05-18 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| EP2359808B1 (en) | 2006-08-09 | 2013-05-22 | Intarcia Therapeutics, Inc | Osmotic delivery systems and piston assemblies |
| CA2677932A1 (en) | 2007-02-15 | 2008-08-21 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| WO2008133908A2 (en) | 2007-04-23 | 2008-11-06 | Intarcia Therapeutics, Inc. | Suspension formulations of insulinotropic peptides and uses thereof |
| MX2010004298A (es) | 2007-10-30 | 2010-05-03 | Univ Indiana Res & Tech Corp | Compuestos que exhiben actividad antagonista de glucagon y agonista de glp-1. |
| ES2509883T3 (es) | 2007-10-30 | 2014-10-20 | Indiana University Research And Technology Corporation | Antagonistas de glucagón |
| CA2726861C (en) | 2008-02-13 | 2014-05-27 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
| CN102105159B (zh) | 2008-06-17 | 2015-07-08 | 印第安纳大学研究及科技有限公司 | 基于gip的混合激动剂用于治疗代谢紊乱和肥胖症 |
| PE20120332A1 (es) | 2008-12-19 | 2012-04-14 | Univ Indiana Res & Tech Corp | Profarmacos de peptido de la superfamilia de glucagon basado en amida |
| EP2443146B1 (en) | 2009-06-16 | 2016-10-05 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
| US9663778B2 (en) | 2009-07-09 | 2017-05-30 | OPKO Biologies Ltd. | Long-acting coagulation factors and methods of producing same |
| RU2547990C2 (ru) | 2009-09-28 | 2015-04-10 | Интарсия Терапьютикс, Инк. | Быстрое достижение и/или прекращение существенной стабильной доставки лекарственного средства |
| JO2976B1 (en) * | 2009-12-22 | 2016-03-15 | ايلي ليلي اند كومباني | Axentomodulin polypeptide |
| KR20120123443A (ko) | 2010-01-27 | 2012-11-08 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 대사 장애 및 비만 치료용 글루카곤 길항제-ｇｉｐ 항진제 콘쥬게이트 |
| MX2012013001A (es) | 2010-05-13 | 2013-02-26 | Univ Indiana Res & Tech Corp | Peptidos de la superfamilia de glucagon que presentan actividad del receptor nuclear de hormonas. |
| JP6050746B2 (ja) | 2010-05-13 | 2016-12-21 | 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 | Ｇタンパク質共役受容体活性を示すグルカゴンスーパーファミリーのペプチド |
| US8507428B2 (en) | 2010-12-22 | 2013-08-13 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting GIP receptor activity |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| US10166295B2 (en) | 2011-06-02 | 2019-01-01 | Opko Biologics Ltd. | Pegylated OXM variants |
| KR102092206B1 (ko) * | 2011-06-02 | 2020-03-24 | 옵코 바이오로직스 리미티드 | 장기-작용성 glp-1/글루카곤 수용체 작용제 |
| UA126465C2 (uk) | 2011-06-10 | 2022-10-12 | Ханмі Сайенс Ко., Лтд. | Пептид, що має активність оксинтомодуліну, та фармацевтична композиція для лікування ожиріння, яка його містить |
| RU2607365C2 (ru) | 2011-06-17 | 2017-01-10 | Ханми Сайенс Ко., Лтд. | Конъюгат, содержащий оксинтомодулин и фрагмент иммуноглобулина, и его применение |
| KR20140043793A (ko) | 2011-06-22 | 2014-04-10 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 글루카곤/glp-1 수용체 공동-작용물질 |
| RS56173B1 (sr) | 2011-06-22 | 2017-11-30 | Univ Indiana Res & Tech Corp | Koagonisti receptora za glukagon/glp-1 receptora |
| JP6324315B2 (ja) | 2011-11-17 | 2018-05-16 | 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 | グルココルチコイド受容体の活性を示すグルカゴンスーパーファミリーのペプチド |
| HK1207564A1 (en) * | 2012-04-19 | 2016-02-05 | Opko Biologics Ltd | Long-acting oxyntomodulin variants and methods of producing same |
| EA201492269A1 (ru) | 2012-06-04 | 2016-02-29 | Опко Байолоджикс Лтд. | Пегилированные варианты oxm |
| CN104583232B (zh) | 2012-06-21 | 2018-04-13 | 印第安纳大学研究及科技有限公司 | 展现gip受体活性的胰高血糖素类似物 |
| KR101968344B1 (ko) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 고지혈증 치료용 조성물 |
| AR092873A1 (es) | 2012-09-26 | 2015-05-06 | Cadila Healthcare Ltd | Peptidos como agonistas triples de los receptores de gip, glp-1 y glugagon |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| KR101993393B1 (ko) | 2012-11-06 | 2019-10-01 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 당뇨병 또는 비만성 당뇨병 치료용 조성물 |
| WO2014073842A1 (en) | 2012-11-06 | 2014-05-15 | Hanmi Pharm. Co., Ltd. | Liquid formulation of protein conjugate comprising the oxyntomodulin and an immunoglobulin fragment |
| AU2013366692B2 (en) | 2012-12-21 | 2017-11-23 | Sanofi | Dual GLP1/GIP or trigonal GLP1/GIP/Glucagon agonists |
| EP2961765A4 (en) * | 2013-03-15 | 2016-11-09 | Adaerata Ltd Partnership | SMALL MOLECULAR PCSK9 MODULATORS AND METHOD OF USE THEREOF |
| US20150158926A1 (en) | 2013-10-21 | 2015-06-11 | Opko Biologics, Ltd. | Long-acting polypeptides and methods of producing and administering same |
| EP3080152A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Non-acylated exendin-4 peptide analogues |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑 |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑 |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| TWI802396B (zh) | 2014-09-16 | 2023-05-11 | 南韓商韓美藥品股份有限公司 | 長效glp-1/高血糖素受體雙促效劑治療非酒精性脂肝疾病之用途 |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| EP3230309B1 (en) | 2014-12-10 | 2023-03-29 | OPKO Biologics Ltd. | Methods of producing long acting ctp-modified growth hormone polypeptides |
| KR102418477B1 (ko) | 2014-12-30 | 2022-07-08 | 한미약품 주식회사 | 글루카곤 유도체 |
| RU2730996C2 (ru) | 2015-06-03 | 2020-08-26 | Интарсия Терапьютикс, Инк. | Системы установки и извлечения имплантата |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| WO2016198624A1 (en) | 2015-06-12 | 2016-12-15 | Sanofi | Exendin-4 derivatives as trigonal glp-1/glucagon/gip receptor agonists |
| WO2016198628A1 (en) | 2015-06-12 | 2016-12-15 | Sanofi | Non-acylated exendin-4 derivatives as dual glp-1/glucagon receptor agonists |
| TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重ｇｌｐ－１／升糖素受體促效劑之新毒蜥外泌肽（ｅｘｅｎｄｉｎ－４）衍生物 |
| TWI622596B (zh) | 2015-10-26 | 2018-05-01 | 美國禮來大藥廠 | 升糖素受體促效劑 |
| KR102574993B1 (ko) | 2016-05-16 | 2023-09-06 | 인타르시아 세라퓨틱스 인코포레이티드 | 글루카곤-수용체 선택적 폴리펩티드 및 이들의 이용 방법 |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| MY206271A (en) | 2016-07-11 | 2024-12-06 | Opko Biologics Ltd | Long-acting coagulation factor vii and methods of producing same |
| TW201832783A (zh) | 2016-12-02 | 2018-09-16 | 法商賽諾菲公司 | 包含ｇｌｐ－１／胰高血糖素雙重激動劑、連接子和透明質酸的接合物 |
| JP7286542B2 (ja) | 2017-01-03 | 2023-06-05 | インターシア セラピューティクス，インコーポレイティド | Ｇｌｐ－１受容体アゴニストの持続的投与及び薬物の同時投与を含む方法 |
| CN108299554B (zh) * | 2017-01-13 | 2021-05-25 | 博瑞生物医药（苏州）股份有限公司 | 胃泌酸调节素类似物 |
| CN106986924A (zh) * | 2017-03-23 | 2017-07-28 | 中国药科大学 | 胃泌酸调节素（oxm）类似物及其应用 |
| US12441776B2 (en) | 2018-11-30 | 2025-10-14 | Eirgen Pharma Ltd. | Oxyntomodulin peptide analog formulations |
| KR102154959B1 (ko) * | 2020-04-29 | 2020-09-10 | 동아에스티 주식회사 | 지속형 glp-1 및 글루카곤 수용체 이중작용제 |
| WO2025169190A2 (en) | 2024-02-06 | 2025-08-14 | Opko Biologics Ltd. | Modified oxyntomodulin and methods of use thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5445090A (en) | 1991-07-25 | 1995-08-29 | Mim Industries, Inc. | Interchangeable clamp for use in a sewing machine |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US6214966B1 (en) | 1996-09-26 | 2001-04-10 | Shearwater Corporation | Soluble, degradable poly(ethylene glycol) derivatives for controllable release of bound molecules into solution |
| US6448369B1 (en) | 1997-11-06 | 2002-09-10 | Shearwater Corporation | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
| JP4078032B2 (ja) | 1998-03-12 | 2008-04-23 | ネクター セラピューティックス エイエル，コーポレイション | 近位の反応性基を持つポリ（エチレングリコール）誘導体 |
| CA2394980C (en) | 1999-12-22 | 2008-05-13 | Shearwater Corporation | Sterically hindered derivatives of water soluble polymers |
| US6413507B1 (en) | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
| US6436386B1 (en) | 2000-11-14 | 2002-08-20 | Shearwater Corporation | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers |
| GB0121709D0 (en) | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| GB0300571D0 (en) | 2003-01-10 | 2003-02-12 | Imp College Innovations Ltd | Modification of feeding behaviour |
| JP2006520818A (ja) | 2003-03-19 | 2006-09-14 | イーライ リリー アンド カンパニー | ポリエチレングリコール結合ｇｌｐ−１化合物 |
| CA2608311C (en) | 2005-05-13 | 2012-11-27 | Eli Lilly And Company | Glp-1 pegylated compounds |
| ATE553124T1 (de) | 2005-06-13 | 2012-04-15 | Imp Innovations Ltd | Oxyntomodulinanaloga und ihre wirkungen auf das fressverhalten |
| CA2913805A1 (en) | 2005-11-07 | 2007-05-18 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| CA2638800A1 (en) * | 2006-02-22 | 2007-09-07 | Merck & Co., Inc. | Oxyntomodulin derivatives |
| TWI428346B (zh) | 2006-12-13 | 2014-03-01 | Imp Innovations Ltd | 新穎化合物及其等對進食行為影響 |
| CA2677932A1 (en) | 2007-02-15 | 2008-08-21 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| EP2158214B1 (en) | 2007-06-15 | 2011-08-17 | Zealand Pharma A/S | Glucagon analogues |
| WO2009030771A1 (en) * | 2007-09-05 | 2009-03-12 | Novo Nordisk A/S | Peptides derivatized with a-b-c-d- and their therapeutical use |
| WO2010096052A1 (en) | 2009-02-19 | 2010-08-26 | Merck Sharp & Dohme Corp. | Oxyntomodulin analogs |
-
2010
- 2010-12-09 AR ARP100104554A patent/AR079344A1/es unknown
- 2010-12-10 TW TW099143355A patent/TWI451873B/zh not_active IP Right Cessation
- 2010-12-15 AU AU2010341650A patent/AU2010341650B2/en not_active Ceased
- 2010-12-15 BR BR112012017054A patent/BR112012017054A2/pt not_active IP Right Cessation
- 2010-12-15 CN CN201080058422.4A patent/CN102665752B/zh active Active
- 2010-12-15 UA UAA201207074A patent/UA106399C2/ru unknown
- 2010-12-15 CA CA2784668A patent/CA2784668C/en active Active
- 2010-12-15 US US12/968,388 patent/US8415296B2/en active Active
- 2010-12-15 SG SG2012046223A patent/SG181872A1/en unknown
- 2010-12-15 ES ES10799178.8T patent/ES2512141T3/es active Active
- 2010-12-15 MX MX2012007449A patent/MX2012007449A/es active IP Right Grant
- 2010-12-15 JP JP2012546033A patent/JP5717758B2/ja active Active
- 2010-12-15 NZ NZ600732A patent/NZ600732A/en not_active IP Right Cessation
- 2010-12-15 PE PE2012000855A patent/PE20121721A1/es not_active Application Discontinuation
- 2010-12-15 EP EP10799178.8A patent/EP2515927B1/en active Active
- 2010-12-15 KR KR1020127016092A patent/KR101399692B1/ko not_active Expired - Fee Related
- 2010-12-15 WO PCT/US2010/060380 patent/WO2011087671A1/en not_active Ceased
- 2010-12-15 EA EA201290557A patent/EA201290557A1/ru unknown
-
2012
- 2012-06-14 TN TNP2012000303A patent/TN2012000303A1/en unknown
- 2012-06-14 MA MA34969A patent/MA33826B1/fr unknown
- 2012-06-20 DO DO2012000175A patent/DOP2012000175A/es unknown
- 2012-06-20 EC ECSP12011988 patent/ECSP12011988A/es unknown
- 2012-06-20 GT GT201200205A patent/GT201200205A/es unknown
- 2012-06-21 CL CL2012001685A patent/CL2012001685A1/es unknown
- 2012-06-21 CO CO12104387A patent/CO6551737A2/es active IP Right Grant
- 2012-06-22 CR CR20120339A patent/CR20120339A/es not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2515927B1 (en) | Oxyntomodulin peptide analogue | |
| EP2515928B1 (en) | Oxyntomodulin peptide analogue | |
| JP7386218B2 (ja) | グルカゴン及びｇｌｐ－１共アゴニスト化合物 | |
| HK1170943B (en) | Oxyntomodulin peptide analogue | |
| HK1170941B (en) | Oxyntomodulin peptide analogue |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |