917910-45-3

MK-6892 is a potent, selective, and full agonist for the high affinity nicotinic acid (NA) receptor GPR109A. Ki and GTPγS EC50 of MK-6892 on the Human GPR109A is 4 nM and 16 nM, respectively.

mk-6892 is a highly potential gpr109a agonists.

despite the increased serum shift of these compounds, the representative 1e was highly potent. furthermore, these compounds had no activity on gpr109b and gpr81, the two most closely related gpcrs with 96% and 50% sequence identity to gpr109a,respectively [1].

na or mk-6892 was orally administered to wt or na receptor null mice on the same c57bl/6 genetic background. after 15 min of 100 mpk dosing of na or mk-6892 to fed wt or na receptor null mice, the blood levels of mk-6892 at 15 min were 229 μm (950-fold greater than the in vitro ec50 determined in mouse na receptor gtpγs assay, which is 240 nm) in wt mice and 148 μm (620-fold greater than the in vitro ec50) in na receptor null mice [1].

ic50 value: 4.0 nm (ki for human gpr109a) [1]

[1] Shen HC, et al. 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
[2] Kim HY, et al. Discovery of 4-(phenyl)thio-1H-pyrazole derivatives as agonists of GPR109A, a high affinity niacin receptor. Arch Pharm Res. 2015 Jun;38(6):1019-32. DOI:10.1007/s12272-015-0560-4