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]
