Target Information

Target General Infomation
Target ID
T93788
Former ID
TTDC00050
Target Name
Glucose-dependent insulinotropic receptor
Gene Name
GPR119
Synonyms
G-protein coupled receptor 119; GPR119
Target Type
Clinical Trial
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T93788
UniProt ID
Q8TDV5
Sequence
MESSFSFGVILAVLASLIIATNTLVAVAVLLLIHKNDGVSLCFTLNLAVADTLIGVAISG
LLTDQLSSPSRPTQKTLCSLRMAFVTSSAAASVLTVMLITFDRYLAIKQPFRYLKIMSGF
VAGACIAGLWLVSYLIGFLPLGIPMFQQTAYKGQCSFFAVFHPHFVLTLSCVGFFPAMLL
FVFFYCDMLKIASMHSQQIRKMEHAGAMAGGYRSPRTPSDFKALRTVSVLIGSFALSWTP
FLITGIVQVACQECHLYLVLERYLWLLGVGNSLLNPLIYAYWQKEVRLQLYHMALGVKKV
LTSFLLFLSARNCGPERPRESSCHIVTISSSEFDG
Drugs and Mode of Action
Drug(s) DS-8500 Drug Info Phase 2 Diabetes [524885]
GSK1292263 Drug Info Phase 2 Gastric cancer; Type 2 diabetes [523205]
SAR-260093 Drug Info Phase 2 Type 2 diabetes [548721]
LEZ763 Drug Info Phase 1/2 Peripheral arterial disease; Type 2 diabetes [523944]
APD-597 Drug Info Phase 1 Type 2 diabetes [522679], [541062]
BMS-903452 Drug Info Phase 1 Type 2 diabetes [523251]
APD668 Drug Info Discontinued in Phase 1 Type 2 diabetes [548256]
PSN821 Drug Info Terminated Type 2 diabetes [550284]
Agonist (R)-N-oleoyltyrosinol Drug Info [530508]
(S)-N-oleoyltyrosinol Drug Info [530508]
1-oleoyl glycerol Drug Info [531569]
1-palmitoyl-lysophosphatidylcholine Drug Info [527346]
1-stearoyl-lysophosphatidylcholine Drug Info [527346]
2-oleoyl glycerol Drug Info [531569]
APD-597 Drug Info [531766]
APD668 Drug Info [551535]
AR231453 Drug Info [528663]
AS-1907417 Drug Info [543393]
AS1269574 Drug Info [531137]
compound 1 Drug Info [531346]
compound 1 Drug Info [531631]
compound 2 Drug Info [531631]
compound 20f Drug Info [531459]
compound 23 Drug Info [531413]
compound 29a Drug Info [531413]
compound 3 Drug Info [531359]
compound 36 Drug Info [531346]
compound 36j Drug Info [531459]
compound 3a Drug Info [531413]
compound 3j Drug Info [531413]
compound 42 Drug Info [531890]
compound 58 Drug Info [531346]
compound 8g Drug Info [531413]
GPR119 agonists Drug Info [543393]
LC34AD3 Drug Info [543393]
lysophosphatidylethanolamine Drug Info [527346]
lysophosphatidylinositol Drug Info [527346]
N-oleoylethanolamide Drug Info [532227]
N-palmitoylethanolamine Drug Info [543393]
oleoyl-lysophosphatidylcholine Drug Info [527346]
PSN375963 Drug Info [528067]
PSN632408 Drug Info [528067]
PSN821 Drug Info [550284]
RO-5212651 Drug Info [543393]
SAR-260093 Drug Info [530406]
SEA Drug Info [543393]
Modulator AR-7947 Drug Info [543393]
BMS-903452 Drug Info [532950]
DS-8500 Drug Info [544477]
GSK1292263 Drug Info
LEZ763 Drug Info
MBX-3254 Drug Info [543393]
Pathways
KEGG Pathway cAMP signaling pathway
Insulin secretion
WikiPathways Incretin Synthesis, Secretion, and Inactivation
References
Ref 522679ClinicalTrials.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 523205ClinicalTrials.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 523251ClinicalTrials.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 523944ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
Ref 524885ClinicalTrials.gov (NCT02222350) Phase 2 Study of DS-8500a in Patients With Type 2 Diabetes. U.S. National Institutes of Health.
Ref 541062(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 548256Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023882)
Ref 548721Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027988)
Ref 550284Clinical pipeline report, company report or official report of Astellas Pharma (2011).
Ref 527346Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem Biophys Res Commun. 2005 Jan 28;326(4):744-51.
Ref 528067Deorphanization 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 528663A 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 530406GPR119 agonists for the treatment of type 2 diabetes. Expert Opin Ther Pat. 2009 Oct;19(10):1339-59.
Ref 530508N-oleoyldopamine enhances glucose homeostasis through the activation of GPR119. Mol Endocrinol. 2010 Jan;24(1):161-70.
Ref 531137Identification 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 531346Design of potent and selective GPR119 agonists for type II diabetes. Bioorg Med Chem Lett. 2011 May 1;21(9):2665-9.
Ref 531359Design 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 531413Bioorg 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 531459Discovery 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 5315692-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J Clin Endocrinol Metab. 2011 Sep;96(9):E1409-17.
Ref 531631Oxidative metabolism of a quinoxaline derivative by xanthine oxidase in rodent plasma. Chem Res Toxicol. 2011 Dec 19;24(12):2207-16.
Ref 531766Discovery 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 531890Use 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 532227Screening 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 532950Discovery 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 543393(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 544477Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31.
Ref 550284Clinical pipeline report, company report or official report of Astellas Pharma (2011).
Ref 551535Announces Initiation of Phase 1 Clinical Trial of Arena Type 2 Diabetes Drug Candidate in Collaboration With Ortho-McNeil. Arena Pharmaceuticals, Inc. FEBRUARY 07, 2006.

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