MK-1903

MK-1903 is a potent and selective small molecule full agonist of hydroxycarboxylic acid receptor 2 (HCA2), also known as GPR109A or the niacin receptor. It exhibits greater potency than niacin in activating HCA2, with an EC50 of 12.9 nM compared to 51 nM for niacin in whole cell assays. MK-1903 shows no binding at the related GRP109B receptor. The drug was developed for oral administration primarily as a cardiovascular therapy targeting dyslipidemia and atherosclerosis by modulating lipid metabolism through HCA2 activation. Development was discontinued after phase II clinical trials due to insufficient efficacy in elevating HDL cholesterol relative to placebo; safety concerns were not cited as reasons for discontinuation[1][2][5][7].