Target Information
Target General Infomation | |||||
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Target ID |
T93788
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Former ID |
TTDC00050
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Target Name |
Glucose-dependent insulinotropic receptor
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Gene Name |
GPR119
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Synonyms |
G-protein coupled receptor 119; GPR119
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Target Type |
Clinical Trial
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Disease | Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1] | ||||
Gastric cancer; Type 2 diabetes [ICD9:151, 250; ICD10: C16, E11] | |||||
Non-insulin dependent diabetes [ICD10: E11.9] | |||||
Peripheral arterial disease; Type 2 diabetes [ICD9:443, 250; ICD10: I73, E11] | |||||
Type 2 diabetes [ICD9: 250; ICD10: E11] | |||||
Function |
Receptor for the endogenous fatty-acid ethanolamide oleoylethanolamide (OEA) and lysophosphatidylcholine (LPC). Functions as a glucose-dependent insulinotropic receptor. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Seems to act through a G(s) mediated pathway.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T93788
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UniProt ID | |||||
Sequence |
MESSFSFGVILAVLASLIIATNTLVAVAVLLLIHKNDGVSLCFTLNLAVADTLIGVAISG
LLTDQLSSPSRPTQKTLCSLRMAFVTSSAAASVLTVMLITFDRYLAIKQPFRYLKIMSGF VAGACIAGLWLVSYLIGFLPLGIPMFQQTAYKGQCSFFAVFHPHFVLTLSCVGFFPAMLL FVFFYCDMLKIASMHSQQIRKMEHAGAMAGGYRSPRTPSDFKALRTVSVLIGSFALSWTP FLITGIVQVACQECHLYLVLERYLWLLGVGNSLLNPLIYAYWQKEVRLQLYHMALGVKKV LTSFLLFLSARNCGPERPRESSCHIVTISSSEFDG |
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Drugs and Mode of Action | |||||
Drug(s) | DS-8500 | Drug Info | Phase 2 | Diabetes | [1] |
GSK1292263 | Drug Info | Phase 2 | Gastric cancer; Type 2 diabetes | [2] | |
SAR-260093 | Drug Info | Phase 2 | Type 2 diabetes | [3] | |
LEZ763 | Drug Info | Phase 1/2 | Peripheral arterial disease; Type 2 diabetes | [4] | |
APD-597 | Drug Info | Phase 1 | Type 2 diabetes | [5], [6] | |
BMS-903452 | Drug Info | Phase 1 | Type 2 diabetes | [7] | |
APD668 | Drug Info | Discontinued in Phase 1 | Type 2 diabetes | [8] | |
PSN821 | Drug Info | Terminated | Type 2 diabetes | [9] | |
Agonist | (R)-N-oleoyltyrosinol | Drug Info | [10] | ||
(S)-N-oleoyltyrosinol | Drug Info | [10] | |||
1-oleoyl glycerol | Drug Info | [11] | |||
1-palmitoyl-lysophosphatidylcholine | Drug Info | [12] | |||
1-stearoyl-lysophosphatidylcholine | Drug Info | [12] | |||
2-oleoyl glycerol | Drug Info | [11] | |||
APD-597 | Drug Info | [13] | |||
APD668 | Drug Info | [14] | |||
AR231453 | Drug Info | [15] | |||
AS-1907417 | Drug Info | [16] | |||
AS1269574 | Drug Info | [17] | |||
compound 1 | Drug Info | [18] | |||
compound 1 | Drug Info | [19] | |||
compound 2 | Drug Info | [19] | |||
compound 20f | Drug Info | [20] | |||
compound 23 | Drug Info | [21] | |||
compound 29a | Drug Info | [21] | |||
compound 3 | Drug Info | [22] | |||
compound 36 | Drug Info | [18] | |||
compound 36j | Drug Info | [20] | |||
compound 3a | Drug Info | [21] | |||
compound 3j | Drug Info | [21] | |||
compound 42 | Drug Info | [23] | |||
compound 58 | Drug Info | [18] | |||
compound 8g | Drug Info | [21] | |||
GPR119 agonists | Drug Info | [16] | |||
LC34AD3 | Drug Info | [16] | |||
lysophosphatidylethanolamine | Drug Info | [12] | |||
lysophosphatidylinositol | Drug Info | [12] | |||
N-oleoylethanolamide | Drug Info | [24] | |||
N-palmitoylethanolamine | Drug Info | [16] | |||
oleoyl-lysophosphatidylcholine | Drug Info | [12] | |||
PSN375963 | Drug Info | [25] | |||
PSN632408 | Drug Info | [25] | |||
PSN821 | Drug Info | [9] | |||
RO-5212651 | Drug Info | [16] | |||
SAR-260093 | Drug Info | [26] | |||
SEA | Drug Info | [16] | |||
Modulator | AR-7947 | Drug Info | [16] | ||
BMS-903452 | Drug Info | [27] | |||
DS-8500 | Drug Info | [28] | |||
GSK1292263 | Drug Info | ||||
LEZ763 | Drug Info | ||||
MBX-3254 | Drug Info | [16] | |||
Pathways | |||||
KEGG Pathway | cAMP signaling pathway | ||||
Insulin secretion | |||||
WikiPathways | Incretin Synthesis, Secretion, and Inactivation | ||||
References | |||||
REF 1 | ClinicalTrials.gov (NCT02222350) Phase 2 Study of DS-8500a in Patients With Type 2 Diabetes. U.S. National Institutes of Health. | ||||
REF 2 | ClinicalTrials.gov (NCT01218204) A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Administering Multiple Oral Doses of GSK1292263 Alone and With Atorvastatin.U.S. National Institutes of Health. | ||||
REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027988) | ||||
REF 4 | ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health. | ||||
REF 5 | ClinicalTrials.gov (NCT00910923) A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-38431055 in Healthy Male Volunteers. U.S. National Institutes of Health. | ||||
REF 6 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5727). | ||||
REF 7 | ClinicalTrials.gov (NCT01240980) Safety Study of BMS-903452 in Healthy Subjects (Panel 1-7) & Relative Bioavailability of the Crystalline and Amorphous Forms of BMS-903452 [Panels 4, 6, 11 & 12(Part A)], and Subjects With Type 2 Diabetes Mellitus (Part B). U.S. National Institutes of Health. | ||||
REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023882) | ||||
REF 9 | Clinical pipeline report, company report or official report of Astellas Pharma (2011). | ||||
REF 10 | N-oleoyldopamine enhances glucose homeostasis through the activation of GPR119. Mol Endocrinol. 2010 Jan;24(1):161-70. | ||||
REF 11 | 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J Clin Endocrinol Metab. 2011 Sep;96(9):E1409-17. | ||||
REF 12 | Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem Biophys Res Commun. 2005 Jan 28;326(4):744-51. | ||||
REF 13 | Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1750-5. | ||||
REF 14 | Announces Initiation of Phase 1 Clinical Trial of Arena Type 2 Diabetes Drug Candidate in Collaboration With Ortho-McNeil. Arena Pharmaceuticals, Inc. FEBRUARY 07, 2006. | ||||
REF 15 | A role for beta-cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucose-dependent insulin release. Endocrinology. 2007 Jun;148(6):2601-9. Epub 2007 Feb 8. | ||||
REF 16 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 126). | ||||
REF 17 | Identification of a novel GPR119 agonist, AS1269574, with in vitro and in vivo glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 2010 Sep 24;400(3):437-41. | ||||
REF 18 | Design of potent and selective GPR119 agonists for type II diabetes. Bioorg Med Chem Lett. 2011 May 1;21(9):2665-9. | ||||
REF 19 | Oxidative metabolism of a quinoxaline derivative by xanthine oxidase in rodent plasma. Chem Res Toxicol. 2011 Dec 19;24(12):2207-16. | ||||
REF 20 | Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes. Bioorg Med Chem Lett. 2011 Jun 1;21(11):3290-6. | ||||
REF 21 | Bioorg Med Chem Lett. 2011 May 15;21(10):3134-41. Epub 2011 Mar 13.Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control. | ||||
REF 22 | Design and evaluation of a 2-(2,3,6-trifluorophenyl)acetamide derivative as an agonist of the GPR119 receptor. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1306-9. | ||||
REF 23 | Use of small-molecule crystal structures to address solubility in a novel series of G protein coupled receptor 119 agonists: optimization of a lead and in vivo evaluation. J Med Chem. 2012 Jun 14;55(11):5361-79. | ||||
REF 24 | Screening beta-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. J Biomol Screen. 2013 Jun;18(5):599-609. | ||||
REF 25 | Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 2006 Mar;3(3):167-75. | ||||
REF 26 | GPR119 agonists for the treatment of type 2 diabetes. Expert Opin Ther Pat. 2009 Oct;19(10):1339-59. | ||||
REF 27 | Discovery of 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an antidiabetic clinical candidate targeting GPR119. J MedChem. 2014 Sep 25;57(18):7499-508. | ||||
REF 28 | Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31. |
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