期刊
BIOORGANIC CHEMISTRY
卷 92, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2019.103209
关键词
Diabetes; FFA1; GPR40; Hyperglycemia; Phenoxyacetic acid
资金
- National Natural Science Foundation of China [81803341]
- Natural Science Foundation of Guangdong Province, China [2018A030313445]
- Innovation and Strong School Project of Guangdong Pharmaceutical University [2017KQNCX111]
- Research Projects of the Chinese Medicine Council of Guangdong Province [20191199]
Based on a previously reported phenoxyacetic acid scaffold, compound 7 (HWL-088) has been identified as a superior free fatty acid receptor 1 (FFA1) agonist by comprehensive structure-activity relationship study. Our results indicated that the introduction of ortho-fluoro greatly increased the activity of phenoxyacetic acid series, and the unique structure-activity relationship in biphenyl moiety is different from previously reported FFA1 agonists. Moreover, the modeling study was also performed to better understand the binding mode of present series. Compound 7 significantly improved glucose tolerance both in normal and diabetic models, and even exerted greater potential on glucose control than that of TAK-875. These findings provided a novel candidate HWL-088, which is currently in preclinical study to evaluate its potential for the treatment of diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据