title: Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist.
abstract: 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.
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Patil
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Aware
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Deshmukh
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Brijesh
authors.initials: B
authors.lastname: Darji
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Sasane
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Kalapatapu V V M
authors.initials: KV
authors.lastname: Sairam
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Priyadarsiny
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Giri
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Harilal
authors.initials: H
authors.lastname: Patel
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Giri
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Mukul
authors.initials: M
authors.lastname: Jain
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
authors.forename: Ranjit C
authors.initials: RC
authors.lastname: Desai
keywords: GLP1 secretion; GPBAR1; GPR 131; TGR5; TGR5 agonist; diabetes
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