Identification of Hydroxybenzoic Acids as Selective Lactate Receptor (GPR81) Agonists with Antilipolytic Effects

被引：44
作者：
Dvorak, Curt A. [1 ]
Liu, Changlu [1 ]
Shelton, Jonathan [1 ]
Kuei, Chester [1 ]
Sutton, Steven W. [1 ]
Lovenberg, Timothy W. [1 ]
Carruthers, Nicholas I. [1 ]
机构：
[1] Janssen Res & Dev LLC, San Diego, CA 92121 USA
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2012年 / 3卷 / 08期
关键词：
lactate receptor; GPR81; HCA1; nicotinic acid receptor; GPR109a; agonist; lipolysis; flushing; FFA; NICOTINIC-ACID; GPR109A;
D O I：
10.1021/ml3000676
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Following the characterization of the lactate receptor (GPR81), a focused screening effort afforded 3-hydroxybenzoic acid 1 as a weak agonist of both GPR81 and GPR109a (niacin receptor). An examination of structurally similar arylhydroxy acids led to the identification of 3-chloro-5-hydroxybenzoic acid 2, a selective GPR81 agonist that exhibited favorable in vivo effects on lipolysis in a mouse model of obesity.
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收藏
页码：637 / 639
页数：3
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