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.
Curt A Dvorak  1 ,  Changlu Liu  1 ,  Jonathan Shelton  1 ,  Chester Kuei  1 ,  Steven W Sutton  1 ,  Timothy W Lovenberg  1 ,  Nicholas I Carruthers  1
Affiliations
  • 1. Janssen Research & Development, LLC , San Diego, California 92121, United States.
PMID: 24900524 DOI: 10.1021/ml3000676
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.
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