BMS-986224

BMS-986224 is a potent, selective, and orally active small molecule agonist of the APJ (apelin) receptor. It was developed by Bristol Myers Squibb for the treatment of chronic heart failure. The drug closely mimics the signaling profile of (Pyr1) apelin-13 but offers improved pharmacokinetics due to its nonpeptidic structure and oral bioavailability. In preclinical studies, BMS-986224 increased stroke volume and cardiac output in animal models without affecting heart rate or preventing cardiac hypertrophy and fibrosis. Its mechanism involves full activation of APJ receptor-mediated pathways including inhibition of cAMP production, stimulation of β-arrestin recruitment, ERK phosphorylation, and receptor internalization[1][5][6][8]. Clinical development for chronic heart failure was discontinued after phase I trials[3].