2. Academic Validation
  3. Identification of an Orally Efficacious GPR40/FFAR1 Receptor Agonist

Identification of an Orally Efficacious GPR40/FFAR1 Receptor Agonist

  • ACS Med Chem Lett. 2016 Sep 21;7(12):1134-1138. doi: 10.1021/acsmedchemlett.6b00331.
Sameer Agarwal 1,  Santosh Sasane 1,  Prashant Deshmukh 1,  Bhadresh Rami 1,  Debdutta Bandyopadhyay 1,  Poonam Giri 1,  Suresh Giri 1,  Mukul Jain 1,  Ranjit C Desai 1
Affiliations

Affiliation

  • 1 Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
PMID: 27994752 DOI: 10.1021/acsmedchemlett.6b00331
Abstract

GPR40/FFAR1 is a G protein-coupled receptor predominantly expressed in pancreatic β-cells and activated by long-chain free fatty acids, mediating enhancement of glucose-stimulated Insulin secretion. A novel series of substituted 3-(4-aryloxyaryl)propanoic acid derivatives were prepared and evaluated for their activities as GPR40 agonists, leading to the identification of compound 5, which is highly potent in in vitro assays and exhibits robust glucose lowering effects during an oral glucose tolerance test in nSTZ Wistar rat model of diabetes (ED50 = 0.8 mg/kg; ED90 = 3.1 mg/kg) with excellent pharmacokinetic profile, and devoid of cytochromes P450 isoform inhibitory activity.

Keywords

FFAR1; GPR40; GPR40 agonist; fatty acids; insulin secretion; type 2 diabetes.

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