BMS-986224 (BMS986224) is a novel potent, selective, orally bioavailable agonist of Apelin receptor (APJ, APLNR) with Ki of 0.074 nM (human APJ).
BMS-986224 is highly selective for the APJ receptor and did not bind other GPCRs at 30 uM concentration.
BMS-986224 showed to be a fully competitive and high-affinity orthosteric ligand, displacing (Pyr1) apelin-13 from the human APJ receptor.
BMS-986224 inhibited forskolin-mediated cAMP production (EC50=0.02 nM), stimulate β-arrestin recruitment, increase ERK phosphorylation, and induce receptor internalization, and EC50 values for monkey, dog, rat, and mouse APJ were similar.
BMS-986224 induces a sustained increase in cardiac output in the cardiac disease setting and exhibits a differentiated profile from the renin-angiotensin system inhibitor enalapril.
