| Literature DB >> 25481394 |
Xuekun Wang1, Tianxiao Zhao1, Baowei Yang2, Zheng Li1, Jian Cui1, Yuxuan Dai1, Qianqian Qiu1, Hao Qiang1, Wenlong Huang3, Hai Qian4.
Abstract
Free fatty acid receptor 1 (FFA1) is a new potential drug target for the treatment of type 2 diabetes because of its role in amplifying glucose-stimulated insulin secretion in pancreatic β-cell. In the present studies, we identified phenoxyacetic acid derivative (18b) as a potent FFA1 agonist (EC50=62.3 nM) based on the structure of phenylpropanoic acid derivative 4p. Moreover, compound 18b could significantly improve oral glucose tolerance in ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6 mice without observation of hypoglycemic side effect. Additionally, compound 18b exhibited acceptable PK profiles. In summary, compound 18b with ideal PK profiles exhibited good activity in vitro and in vivo, and might be a promising drug candidate for the treatment of diabetes mellitus.Entities:
Keywords: FFA1 agonist; Oral glucose tolerance test; Phenoxyacetic acid; β-oxidation
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Year: 2014 PMID： 25481394 DOI： 10.1016/j.bmc.2014.11.016
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641