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

Curt A Dvorak; Changlu Liu; Jonathan Shelton; Chester Kuei; Steven W Sutton; Timothy W Lovenberg; Nicholas I Carruthers

doi:10.1021/ml3000676

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

ACS Med Chem Lett. 2012 Jun 11;3(8):637-9. doi: 10.1021/ml3000676. eCollection 2012 Aug 9.

Authors

Curt A Dvorak¹, Changlu Liu¹, Jonathan Shelton¹, Chester Kuei¹, Steven W Sutton¹, Timothy W Lovenberg¹, Nicholas I Carruthers¹

Affiliation

¹ Janssen Research & Development, LLC , San Diego, California 92121, United States.

Abstract

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.

Keywords: FFA; GPR109a; GPR81; HCA1; agonist; flushing; lactate receptor; lipolysis; nicotinic acid receptor.