Novel small molecule agonist of TGR5 possesses anti-diabetic effects but causes gallbladder filling in mice

PLoS ONE

Volumn 10, Issue 8, 2015, Pages

  Briere, Daniel A ^a   Ruan, Xiaoping ^a   Cheng, Christine C ^a   Siesky, Angela M ^a   Fitch, Thomas E ^a   Dominguez, Carmen ^b   Sanfeliciano, Sonia Gutierrez ^b   Montero, Carlos ^b   Suen, Chen S ^a,c   Xu, Yanping ^a   Coskun, Tamer ^a   Michael, M Dodson ^a  

^a ELI LILLY AND COMPANY   (United States)

^b ELI LILLY AND COMPANY   (Spain)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; G PROTEIN COUPLED RECEPTOR; GLUCAGON LIKE PEPTIDE 1; PEPTIDE YY; PROTEIN TGR5; SITAGLIPTIN; TGR5 STIMULATING AGENT; UNCLASSIFIED DRUG; GPBAR1 PROTEIN, HUMAN; GPBAR1 PROTEIN, MOUSE; MOLECULAR LIBRARY;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIDIABETIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG SELECTIVITY; ENTEROENDOCRINE CELL; GALLBLADDER DISEASE; HUMAN; HUMAN TISSUE; MALE; MOUSE; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PROTEIN SECRETION; RISK BENEFIT ANALYSIS; SINGLE DRUG DOSE; WEIGHT REDUCTION; AGONISTS; ANIMAL; C57BL MOUSE; CHEMISTRY; DRUG EFFECTS; GALLBLADDER; GENE EXPRESSION REGULATION; GENETICS; GLUCOSE TOLERANCE TEST; HEK293 CELL LINE; KNOCKOUT MOUSE; MOLECULAR LIBRARY; PATHOPHYSIOLOGY; PHARMACOLOGY; PRECLINICAL STUDY; PROCEDURES; SECRETION (PROCESS);

ANIMALS; DRUG EVALUATION, PRECLINICAL; GALLBLADDER; GENE EXPRESSION REGULATION; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE TOLERANCE TEST; HEK293 CELLS; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MICE, INBRED C57BL; MICE, KNOCKOUT; PEPTIDE YY; RECEPTORS, G-PROTEIN-COUPLED; SMALL MOLECULE LIBRARIES; WEIGHT LOSS;

EID: 84943222848     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0136873     Document Type: Article

References (31)

1. Bayliss W, Starling E (1902) On the causation of the so-called 'peripheral reflex secretion' of the pancreas. Proceedings of the Royal Society of London 69: 352-353.
2. Elrick H, Stimmler L, Hlad CJ Jr, Arai Y (1964) Plasma Insulin Response to Oral and Intravenous Glucose Administration. J Clin Endocrinol Metab 24: 1076-1082. PMID: 14228531
3. Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132: 2131-2157. PMID: 17498508
4. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368: 1696-1705. PMID: 17098089
5. Batterham RL, Bloom SR (2003) The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci 994: 162-168. PMID: 12851312
6. Vrang N, Madsen AN, Tang-Christensen M, Hansen G, Larsen PJ (2006) PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 291: R367-375. PMID: 16914421
7. Neary NM, Small CJ, Druce MR, Park AJ, Ellis SM, et al. (2005) Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively. Endocrinology 146: 5120-5127. PMID: 16150917
8. Talsania T, Anini Y, Siu S, Drucker D, Brubaker P (2005) Peripheral Exendin-4 and Peptide YY3-36 Synergistically Reduce Food Intake through Different Mechanisms in Mice. Endocrinology 146: 3748-3756. PMID: 15932924
9. Diakogiannaki E, Gribble FM, Reimann F (2012) Nutrient detection by incretin hormone secreting cells. Physiol Behav 106: 387-393. doi: 10.1016/j.physbeh.2011.12.001 PMID: 22182802
10. Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K (2008) Targeting bile-acid signaling for metabolic diseases. Nature Reviews Drug Discovery 7: 678-693. doi: 10.1038/nrd2619 PMID: 18670431
11. Thomas C, Auwerx J, Schoonjans K (2008) Bile Acids and the Membrane Bile Acid Receptor TGR5-Connecting Nutrition and Metabolism. Thyroid 18: 167-174. doi: 10.1089/thy.2007.0255 PMID: 18279017
12. Houten SM, Auwerx J (2004) The enterohepatic nuclear receptors are major regulators of the enterohepatic circulation of bile salts. Ann Med 36: 482-491. PMID: 15513299
13. Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, et al. (2002) Identification of membranetype receptor for bile acids (M-BAR). Biochem Biophys Res Commun 298: 714-719. PMID: 12419312
14. Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, et al. (2003) A G protein-coupled receptor responsive to bile acids. J Biol Chem 278: 9435-9440. PMID: 12524422
15. Vassileva G, Golovko A, Markowitz L, Abbondanzo SJ, Zeng M, et al. (2006) Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem J 398: 423-430. PMID: 16724960
16. Reimann F, Ward P, Gribble F (2006) Signaling Mechanisms Underlying the Release of Glucagon-Like Peptide 1. Diabetes 55: S78-S85.
17. Katsuma S, Hirasawa A, Tsujimoto G (2005) Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun 329: 386-390. PMID: 15721318
18. Engelstoft MS, Egerod KL, Holst B, Schwartz TW (2008) A gut feeling for obesity: 7TM sensors on enteroendocrine cells. Cell Metab 8: 447-449. doi: 10.1016/j.cmet.2008.11.004 PMID: 19041758
19. Glicksman C, Pournaras DJ, Wright M, Roberts R, Mahon D, et al. (2010) Postprandial plasma bile acid responses in normal weight and obese subjects. Ann Clin Biochem 47: 482-484. doi: 10.1258/acb. 2010.010040 PMID: 20595403
20. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, et al. (2006) Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439: 484-489. PMID: 16400329
21. Pellicciari R, Gioiello A, Macchiarulo A, Thomas C, Rosatelli E, et al. (2009) Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity. J Med Chem 52: 7958-7961. doi: 10.1021/jm901390p PMID: 20014870
22. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, et al. (2009) TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 10: 167-177. doi: 10.1016/j.cmet.2009.08.001 PMID: 19723493
23. Keitel V, Cupisti K, Ullmer C, Knoefel W, Kubitz R, et al. (2009) The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders. Hepatology 50: 861-870. doi: 10.1002/hep.23032 PMID: 19582812
24. Li T, Holmstrom SR, Kir S, Umetani M, Schmidt DR, et al. (2011) The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling. Mol Endocrinol 25: 1066-1071. doi: 10.1210/me.2010-0460 PMID: 21454404
25. Rindi G, Grant SG, Yiangou Y, Ghatei MA, Bloom SR, et al. (1990) Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression. Am J Pathol 136: 1349-1363. PMID: 2162628
26. Tiwari A, Maiti P (2009) TGR5: an emerging bile acid G-protein-coupled receptor target for the potential treatment of metabolic disorders. Drug Discov Today 14: 523-530. doi: 10.1016/j.drudis.2009.02.005PMID: 19429513
27. Jansen PL (2010) A new life for bile acids. J Hepatol 52: 937-938. doi: 10.1016/j.jhep.2010.02.003 PMID: 20392510
28. Duan H, Ning M, Chen X, Zou Q, Zhang L, et al. (2012) Design, synthesis, and antidiabetic activity of 4-phenoxynicotinamide and 4-phenoxypyrimidine-5-carboxamide derivatives as potent and orally efficacious TGR5 agonists. J Med Chem 55: 10475-10489. doi: 10.1021/jm301071h PMID: 23148522
29. Zambad SP, Tuli D, Mathur A, Ghalsasi SA, Chaudhary AR, et al. (2013) TRC210258, a novel TGR5 agonist, reduces glycemic and dyslipidemic cardiovascular risk in animal models of diabesity. Diabetes Metab Syndr Obes 7: 1-14. doi: 10.2147/DMSO.S50209 PMID: 24379686
30. Phillips D, Gao W, Yang Y, Zhang G, Lerario I, et al. (2014) Discovery of Trifluoromethyl(pyrimidin-2-yl) azetidine-2-carboxamides as Potent, Orally Bioavailable TGR5 (GPBAR1) Agonists: Structure-Activity Relationships, Lead Optimization and Chronic In Vivo Efficacy. J Med Chem 58: 3263-3282.
31. Zou Q, Duan H, Ning M, Liu J, Feng Y, et al. (2014) 4-Benzofuranyloxynicotinamide derivatives are novel potent and orally available TGR5 agonists. European Journal of Medicinal Chemistry 82: 1-15. doi: 10.1016/j.ejmech.2014.05.031 PMID: 24863981