Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist

TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorabl...

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Bibliographic Details
Published in:	ACS medicinal chemistry letters Vol. 7; no. 1; pp. 51 - 55
Main Authors:	Agarwal, Sameer, Patil, Amit, Aware, Umesh, Deshmukh, Prashant, Darji, Brijesh, Sasane, Santosh, Sairam, Kalapatapu V. V. M, Priyadarsiny, Priyanka, Giri, Poonam, Patel, Harilal, Giri, Suresh, Jain, Mukul, Desai, Ranjit C
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 14-01-2016
Subjects:	Letter GPR 131 TGR5 GPBAR1 GLP1 secretion TGR5 agonist diabetes
Online Access:	Get full text
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Summary:	TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound 6g was found to have potent glucose lowering effects in vivo during an oral glucose tolerance test in DIO C57 mice with ED50 of 7.9 mg/kg and ED90 of 29.2 mg/kg.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1948-5875 1948-5875
DOI:	10.1021/acsmedchemlett.5b00323