Identification of hydroxybenzoic acids as selective lactate receptor (GPR81) agonists with antilipolytic effects

ACS Medicinal Chemistry Letters

Volumn 3, Issue 8, 2012, Pages 637-639

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

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

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

Indexed keywords

3 CHLORO 5 HYDROXYBENZOIC ACID; 3 HYDROXYBENZOIC ACID; AGENTS AFFECTING LIPID METABOLISM; HYDROXYBENZOIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG SCREENING; IN VIVO STUDY; LIPOLYSIS; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL;

EID: 84865039701     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml3000676     Document Type: Article

References (12)

1. Ahmed, K.; Tunaru, S.; Offermanns, S. GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors Trends Pharmacol. Sci. 2009, 30, 557-562
2. Tunaru, S.; Kero, J.; Schaub, A.; Wufka, C.; Blaukat, A.; Pfeffer, K.; Offermanns, S. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect Nat. Med. (N. Y., NY, U. S.) 2003, 9, 352-355 (Pubitemid 36362793)
3. Wise, A.; Foord, S. M.; Fraser, N. J.; Barnes, A. A.; Elshourbagy, N.; Eilert, M.; Ignar, D. M.; Murdock, P. R.; Steplewski, K.; Green, A.; Brown, A. J.; Dowell, S. J.; Szekeres, P. G.; Hassall, D. G.; Marshall, F. H.; Wilson, S.; Pike, N. B. Molecular identification of high and low affinity receptors for nicotinic acid J. Biol. Chem. 2003, 278, 9869-9874 (Pubitemid 36800490)
4. Benyo, Z.; Gille, A.; Kero, J.; Csiky, M.; Suchankova, M. C.; Nuesing, R. M.; Moers, A.; Pfeffer, K.; Offermanns, S. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing J. Clin. Invest. 2005, 115, 3634-3640 (Pubitemid 43121852)
5. Benyo, Z.; Gille, A.; Bennett, C. L.; Clausen, B. E.; Offermanns, S. Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells Mol. Pharmacol. 2006, 70, 1844-1849 (Pubitemid 44771899)
6. Liu, C.; Wu, J.; Zhu, J.; Kuei, C.; Yu, J.; Shelton, J.; Sutton, S. W.; Li, X.; Yun, S. J.; Mirzadegan, T.; Mazur, C.; Kamme, F. Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81 J. Biol. Chem. 2009, 284 (5) 2811-2822
7. Boatman, P. D.; Johnson, B. R.; Jung, J.-K.; Kasem, M.; Schrader, T. O.; Skinner, P. J.; Colletti, S. L. Preparation of 3H-imidazo[4,5-b]pyridin-5-ol derivatives useful in the treatment of GPR81 receptor disorders. WO2010030360A1.
8. Kuei, C.; Yu, J.; Zhu, J.; Wu, J.; Zhang, L.; Shih, A.; Mirzadegan, T.; Lovenberg, T.; Liu, C. Study of GPR81, the lactate receptor, from distant species identifies residues and motifs critical for GPR81 functions Mol. Pharmacol. 2011, 80, 848-858
9. Liu, C.; Kuei, C.; Zhu, J.; Yu, J.; Zhang, L.; Shih, A.; Mirzadegan, T.; Shelton, J.; Sutton, S.; Connelly, M. A.; Lee, G.; Carruthers, N.; Wu, J.; Lovenberg, T. W. 3,5-Dihydroxybenzoic Acid, a Specific Agonist for HCA1, Inhibits Lipolysis in Adipocytes J. Pharmacol. Exp. Ther. 2012, 341, 794-801
10. Ren, N.; Kaplan, R.; Hernandez, M.; Cheng, K.; Jin, L.; Taggart, A. K. P.; Zhu, A. Y.; Gan, X.; Wright, S. D.; Cai, T.-Q. Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G) J. Lipid Res. 2009, 50, 908-914
11. Boatman, P. D.; Schrader, T. O.; Kasem, M.; Johnson, B. R.; Skinner, P. J.; Jung, J.-K.; Xu, J.; Cherrier, M. C.; Webb, P. J.; Semple, G.; Sage, C. R.; Knudsen, J.; Chen, R.; Taggart, A. K.; Carballo-Jane, E.; Richman, J. G. Potent tricyclic pyrazole tetrazole agonists of the nicotinic acid receptor (GPR109a) Bioorg. Med. Chem. Lett. 2010, 20, 2797-2800
12. Liu, C.; Eriste, E.; Sutton, S.; Chen, J.; Roland, B.; Kuei, C.; Farmer, N.; Joernvall, H.; Sillard, R.; Lovenberg, T. W. Identification of Relaxin-3/INSL7 as an Endogenous Ligand for the Orphan G-protein-coupled Receptor GPCR135 J. Biol. Chem. 2003, 278, 50754-50764 (Pubitemid 37548924)