Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate.

Article Details

Citation

Shen HC, Ding FX, Raghavan S, Deng Q, Luell S, Forrest MJ, Carballo-Jane E, Wilsie LC, Krsmanovic ML, Taggart AK, Wu KK, Wu TJ, Cheng K, Ren N, Cai TQ, Chen Q, Wang J, Wolff MS, Tong X, Holt TG, Waters MG, Hammond ML, Tata JR, Colletti SL

Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate.

J Med Chem. 2010 Mar 25;53(6):2666-70. doi: 10.1021/jm100022r.

PubMed ID
20184326 [ View in PubMed
]
Abstract

Biaryl cyclohexene carboxylic acids were discovered as full and potent niacin receptor (GPR109A) agonists. Compound 1e (MK-6892) displayed excellent receptor activity, good PK across species, remarkably clean off-target profiles, good ancillary pharmacology, and superior therapeutic window over niacin regarding the FFA reduction versus vasodilation in rats and dogs.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
NiacinHydroxycarboxylic acid receptor 2Ki (nM)82N/AN/ADetails
NiacinHydroxycarboxylic acid receptor 2Ki (nM)104N/AN/ADetails
NiacinHydroxycarboxylic acid receptor 2EC 50 (nM)527N/AN/ADetails