GPR119 agonists as potential new oral agents for the treatment of type 2 diabetes and obesity

Expert Opinion on Drug Discovery

Volumn 3, Issue 4, 2008, Pages 403-413

  Fyfe, Matthew C T ^a   McCormack, James G ^a   Overran, Hilary A ^a   Procter, Martin J ^a   Reynet, Christine ^a  

^a Prosidion Limited   (United Kingdom)

Author keywords

Antidiabetic agents; Antiobesity agents; GLP 1; GPR119

Indexed keywords

1 DEOXY 3 (1,1 DIMETHYLBUTYL) DELTA8 TETRAHYDROCANNABINOL; 2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; AGENTS AFFECTING METABOLISM; ANANDAMIDE; ANTIDIABETIC AGENT; ANTIOBESITY AGENT; APD 119; AR 231453; DP IV INHIBITOR; ETHANOLAMIDE DERIVATIVE; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 119; G PROTEIN COUPLED RECEPTOR 119 AGONIST; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOSE; INCRETIN; INSULIN; LEPTIN; METHANANDAMIDE; N OLEOYLDOPAMINE; N OLEOYLETHANOLAMINE; OLVANIL; ORAL ANTIDIABETIC AGENT; PALMIDROL; PSN 119 1; PSN 375963; PSN 632408; PSN 821; UNINDEXED DRUG;

CONCENTRATION RESPONSE; DIABETES CONTROL; DRUG ABSORPTION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG RESPONSE; DRUG STRUCTURE; FOOD INTAKE; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCEMIC CONTROL; HORMONE BLOOD LEVEL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; INSULIN RELEASE; INTESTINE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEOTIDE SEQUENCE; OBESITY; PANCREAS; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN LOCALIZATION; REVIEW; STRUCTURE ACTIVITY RELATION; TREATMENT DURATION; WEIGHT REDUCTION;

EID: 42949149706     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.3.4.403     Document Type: Review

References (59)

1. Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab 2004;89:2522-5
2. Bailey CJ. Drugs on the horizon for diabesity. Curr Diab Rep 2005;5:353-9
3. Cefalu WT, Waldman S, Ryder S. Pharmacotherapy for the treatment of patients with type 2 diabetes mellitus: Rationale and specific agents. Clin Pharmacol Ther 2007;81:636-49
4. Krentz AJ, Bailey CJ. Oral antidiabetic agents. Current role in Type 2 diabetes mellitus. Drugs 2005;65:385-411
5. Overington J, Al-Lazikani PB, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006;5:993-6
6. Schlyer S, Horuk R. I want a new drug: G-protein-coupled receptors in drug development. Drug Discov Today 2006;11:481-93
7. Bjenning C, Al-Shamma H, Thomsen W, et al. G protein-coupled receptors as therapeutic targets for obesity and type 2 diabetes. Curr Opin Invest Drugs 2004;5:1051-62
8. Schiöth HR. G protein-coupled receptors in regulation of body weight. CNS Neurol Disorders Drug Targets 2006;5:241-9
9. Fyfe MCT, Overton HA, Procter MJ, et al. New nonpeptide-binding GPCRs as targets for diabetes and the metabolic syndrome. Annu Rep Med Chem 2007;42:129-45
10. Morphy R. The influence of target family and functional activity on the physicochemical properties of pre-clinical compounds. J Med Chem 2006;49:2969-78
11. Fredriksson R, Höglund PJ, Gloriam DEI, et al. Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett 2003;554:381-8
12. Bonini JA, Borowsky BE, Adham N, et al. DNA encoding SNORF25 receptor. US6221660 (2001)
13. Bonini JA, Borowsky BE, Adham N, et al. Methods of identifying compounds that bind to SNORF25 receptors. US6468756 (2002)
14. Jones RM, Semple G, Fioravanti B, et al. 1,2,3-trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycaemia. WO2004065380 (2004)
15. Takeda S, Kadowaki S, Haga T, et al. Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett 2002;520:97-101
16. Davey J. G-protein-coupled receptors: new approaches to maximise the impact of GPCRs in drug discovery. Exp Opin Ther Targets 2004;8:165-70
17. Griffin G. Methods for identification of modulators of OSGPR116 activity. US7083933 (2006)
18. Chu Z, Carroll C, Gutierrez V, et al. AR231453 mediates improved glycaemic control exclusively via GDIR/GPR119. Keystone Symposium [abstract 117]. Diabetes: Molecular Genetics, Signalling Pathways and Integrated Physiology. Keystone, Colorado, USA; 2007
19. Chu Z, Jones R, Chen R, et al. Novel lipid amide activators of GDIR/ GPR119 and their role in glucose homeostasis [abstract 230]. Keystone Symposium. Diabetes: Molecular Genetics, Signalling Pathways and Integrated Physiology. Keystone, Colorado, USA; 2007
20. Ohishi T, Takasaki J, Matsumoto M, et al. Method of screening remedy for diabetes. EP1338651 (2003)
21. Overton HA, Fyfe MCT, Reynet C. GPR119, a novel G-protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br J Pharrnacol 2007: published online 26 November 2007, doi:10.1038/ sj.bpj.0707529
22. Fyfe MCT, Overton HA, White JR, et al. Discovery of novel, orally active, synthetic GPR119 agonists as potential agents for treatment of obesity and associated metabolic disorders. Diabetes 2006;55(Suppl 1):346-OR
23. Soga T, Ohishi T, Matsui T, et al. Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem Biophys Res Commun 2005;326:744-51
24. Chu Z-L, Leonard JN, Al-Shamma HA, Jones RM. Combination therapy for the treatment of diabetes and conditions related thereto and for the treatment of conditions ameliorated by increasing a blood GLP-1 level. WO2006076231 (2006)
25. Chu Z-L, Jones RM, He H, et al. A role for β-cell-expressed GPR119 in glycemic control by enhancing glucose-dependent insulin release. Endocrinology 2007;148:2601-9
26. Sakamoto Y, Inoue H, Kawakami S, et al. Expression and distribution of GPR119 in the pancreatic islets of mice and rats: predominant localization in pancreatic polypeptide-secreting PP-cells. Biochem Biophys Res Commun 2006;351:474-80
27. Fyfe MCT, White J, Widdowson PS, et al. GPR119 agonists are potential novel oral agents for the treatment of diabesity. Diabetes 2007;56(Suppl 1):532-P
28. Drucker DJ, Jin T, Asa SL, et al. Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enterondocrine cell line. Mol Endocrinol 1994;8:1646-55
29. Overton HA, Babbs AJ, Doel SM, et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 2006;3:167-75
30. Fujimoto WY, Metz SA. Phasic effects of glucose, phospholipase A2 and lysophospholipids on insulin secretion. Endocrinology 1987;120:1750-7
31. Rodríguez de Fonseca FR, Navarro M, Gómez R, et al. An anorexic lipid mediator regulated by feeding. Nature 2001;414:209-12
32. Fu J, Gaetani S, Oveisi F, et al. Oleoylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α. Nature 2003;425:90-3
33. Proulx K, Cota D, Castaneda TR, et al. Mechanisms of oleoylethanolamide (OEA)-induced changes in feeding behaviour and motor activity. Am J Physiol 2005;289:R729-37
34. Yang Y, Chen M, Georgeson KE, Harmon CM. Mechanism of oleoylethanolamide on fatty acid uptake in small intestine after food intake and body weight reduction. Am J Physiol 2007;292:R235-41
35. Fyfe MCT, Babbs AJ, Bertram LS, et al. Synthesis, SAR, and in vivo efficacy of novel GPR119 agonists with a 4-[3-(4-methanesulfinylphenoxy) propyl]-1-Boc-piperidine core. Abstr Papers 234th National ACS Meeting; 2007 August 19 - 23; Boston, MA, USA; MEDI-062
36. Furman B, Pyne N, Flatt P, O'Harte F. Targeting beta-cell cyclic 3′5′ adenosine monophosphate for the development of novel drugs for treating type 2 diabetes mellitus. A review. J Pharm Pharmacol 2004;56:1477-92
37. Lan H, Vassileva G, Corona A, et al. Mice lacking GPR119 maintain metabolic homeostasis [abstract 253]. Keystone Symposium. Diabetes: Molecular Genetics, Signalling Pathways and Integrated Physiology. Keystone, Colorado, USA; 2007
38. Brubaker PL, Schloos J, Drucker DJ. Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line. Endocrinology 1998;139:4108-14
39. Jones RM. Discovery of agonists of the glucose dependent insulinotropic receptor, GPR119, a pancreatic beta-cell oGPCR, for the treatment of NIDDM Abstr Papers 232nd National ACS Meeting; 2006 September 10 - 14; San Francisco, CA, USA; MEDI-275
40. Drucker DJ. Development of glucagon-like peptide-1-based pharmaceuticals as therapeutic agents for the treatment of diabetes. Curr Pharmaceut Des 2001;7:1399-412
41. Meier JJ, Nauck MA, Schmidt WE, Gallwitz B. Gastric inhibitory polypeptide: the neglected incretin revisited. Regul Pept 2002;107:1-13
42. Gromada J, Brock B, Schmitz O, Rorsman P. Glucagon-like peptide-1: regulation of insulin secretion and therapeutic potential. Basic Clin Pharmacol Toxicol 2004;95:252-62
43. Holst JJ, Deacon CF. Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia 2005;48:612-5
44. Holst JJ. Glucagon-like peptide-1: from extract to agent. Diabetologia 2006;49:253-60
45. Drucker DJ. The biology of incretin hormones. Cell Metab 2006;3:153-65
46. Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest 2007;117:24-32
47. Brubaker PL, Drucker DJ. Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut and central nervous system. Endocrinology 2004;145:2653-9
48. Koh G, Suh KS, Chon S, et al. Elevated cAMP level attenuates 2-deoxy-D-ribose induced oxidative damage in pancreatic beta-cells. Arch Biochem Biophys 2005;438:70-9
49. Kwon G, Pappan KL, Marshall CA, et al. cAMP dose-dependently prevents palmitate-induced apoptosis by both protein kinase A and cAMP-guanine nucleotide exchange factor-dependent pathways in β-cells. J Biol Chem 2004;279:8938-45
50. Fyfe MCT, Widdowson P. Use of GPCR agonists to prevent progression of diabetes. WO2007138362 (2007)
51. Meier JJ, Gallwitz B, Schmidt WE, Nauck MA. Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives. Eur J Pharmacol 2002;440:269-79
52. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824-30
53. Nielsen LL. Incretin mimetics and DPP-IV inhibitors for the treatment of type 2 diabetes. Drug Discov Today 2005;10:703-10
54. Madiraju SRM, Poitout V. GPCRs and insulin secretion: 119 and counting. Endocrinology 2007;148:2598-600
55. Mealy NE, Lupone B. Endocrine disorders. Drugs Fut 2006;31:719-50
56. Unniappan S, Mcintosh CH, Demuth HU, et al. Effects of dipeptidyl peptidase IV on the satiety actions of peptide YY. Diabetologia 2006;49:1915-23
57. Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type 2 diabetes mellitus. J Clin Invest 1993;91:301-7
58. Højberg PV, Vilsbøll T, Knop FK, et al. Four weeks of near-normalization of blood glucose restores the insulin response to GIP and improves the insulin response to GLP-1 in patients with type 2 diabetes. Diabetes 2007;56(Suppl 1):1455-P
59. Chu Z-L, Carroll C, Alfonso J, et al. A role for intestinal endocrine cell-expressed GPR119 in glycemic control by enhancing GLP-1 and GIP release. Endocrinology 2008: published online 17 January 2008, doi:10.1210/en.2007-0966