Biological Activity
mk-2894 is a highly potent and selective inhibitor of ep4 receptor with ic50 value of 2.5 nm [1].mk-2894 is a highly selective and potent second generation ep4 antagonist with a ki of 0.56±0.1nm in the radio ligand binding assay using membranes prepared from human ep1-4 overexpressed hek 293 cell lines. and the ep4 functional assay measures the inhibition of pge2-induced camp accumulation with ic50 of 2.5±0.7nm. in the aia model and gi tolerability model in male sd rats, mk-2894 shows a dose-dependent inhibition of pain response with ed50 of 0.36 mg/kg. it also has the potent activity in inhibiting chronic pawswelling with ed50 of 0.02 mg/kg/day. overall, mk-2894 displays the desired potency, selectivity, pharmacokinetic, and gi tolerability profile for further development and represents a potential safer alternative for treating pain and inflammation than traditional nsaids and coxibs [1].
References
[1] marc blouin, yongxin han, jason burch, julie farand, christophe mellon, mireille gaudreault, mark wrona, jean-francois levesque, danielle denis, marie-claude mathieu, rino stocco, erika vigneault, alex therien, patsy clark, steve rowland, daigen xu, gary o’neill, yves ducharme and rick friesen. the discovery of 4-{1-[({2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]cyclopropyl}benzoic acid (mk-2894), a potent and selective prostaglandin e2 subtype 4 receptor antagonist. j. med. chem. 2010, 53: 2227–2238.
