BMS-986331

BMS-986331 is an orally active selective N-Formyl Peptide Receptor 2 (FPR2) agonist with an EC 50 of 0.5 nM in humans and 1 nM in rats. BMS-986331 activates Gαi2, GαoA, Gα12, Gα13 signaling pathways, recruits β-arrestin1 and β-arrestin2, and inhibits downstream cAMP. BMS-986331 induces the expression and release of the pro-resolution cytokine IL-10. BMS-986331 improves cardiac structure and function in a rat model of heart failure induced by permanent coronary artery occlusion. BMS-986331 can be used for the research of heart failure ^[1].

In Vivo, BMS-986331 (Compound 16) (10 mg/kg; p.o.; single dose) induces a 105% increase in plasma IL-10 levels in LPS-challenged rats^[1]. BMS-986331 (0.1-10 mg/kg/day; p.o.; once daily; 6 weeks) preserves infarct wall thickness and improves left ventricular ejection fraction in rats with permanent coronary artery occlusion^[1].

In Vitro, BMS-986331 (Compound 16) potently activates human FPR2 (hFPR2) with an EC50 of 0.5 nM and exhibits 500-fold selectivity over hFPR1; it also activates rat FPR2 with an EC50 of 0.6 nM and 280-fold selectivity over rat FPR1^[1]. BMS-986331 shows high chemical stability at pH 1, with a half-life > 500 min^[1]. BMS-986331 (100 nM) induces a 211% increase in IL-10 levels in human whole blood^[1]. BMS-986331 potently activates multiple signaling pathways via human FPR2 in HEK293 cells, with EC50 values of 0.50 nM for Gαi2, 0.56 nM for GαoA, 16 nM for Gα12/P115, and 40 nM for Gα13/PDZ-RhoGEF^[1]. BMS-986331 induces the recruitment of β-arrestin1 and β-arrestin2 to human FPR2 in HEK293 cells, with EC50 values of 46 nM for β-arrestin1 and 19 nM for β-arrestin2^[1]. BMS-986331 inhibits OATP1B3 with an IC₅₀ of 12 μM^[1]. BMS-986331 retains 88% of its concentration in human liver microsomes and 33% in rat liver microsomes after incubation^[1].

References:
[1]. Shirude PS, et al. From Lead to Clinical Candidate: Discovery of BMS-986331 as a Potent and Selective N -Formyl Peptide Receptor 2 Agonist. J Med Chem. 2026;69(4):4078-4089.