BMS-986224 (C09-1113-200)

BMS-986224 is a potent, selective and orally active APJ receptor agonist ( K d = 0.3 nM). BMS-986224 exhibits similar receptor binding and signaling profile to (Pyr 1 ) apelin-13. BMS-986224 has the potential for the research of heart failureIn VitroBMS-986224 fully inhibits forskolin-mediated cAMP production, with an EC 50 for human APJ of 0.02 nM. BMS-986224 (0-100 nM) fully stimulates β-arrestin recruitment, ERK phosphorylation, and APJ internalization in Chinese hamster ovary-K1 or HEK293 ZF cells. BMS-986224 is a potent and selective APJ receptor agonist that exhibits a similar signaling profile to (Pyr1) apelin-13. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoBMS-986224 (0.192 mg/kg or 3 mg/kg; SC infusion; daily;) in the RHR model increased stroke volume and cardiac output to levels seen in healthy animals but without preventing cardiac hypertrophy and fibrosis, effects differentiated from enalapril . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Sprague-Dawley rats (renal hypertensive rat model) Dosage: 0.192 mg/kg or 3 mg/kg Administration: SC infusion; daily; Initiated 3 days before surgery and continued for 7 days after surgery Result: The achieved steady-state plasma concentrations during 10-day infusion were 102 and 2686 nmol/L at low dose and HD, respectively. At the low dose, BMS-986224 increased SV and CO without affecting other measured parameters, including the measured diastolic parameters, cardiac fibrosis, and heart weight in RHR.Form:SolidIC50& Target:Kd: 0.3 nM (APJ receptor). Specification: 0.98 Molecular Formula: C24H23ClN4O6 Molecular Weight: 498.92 PubChem CID: 137106310 Isomeric SMILES: CCOCC1=C(C(=C(C(=O)N1)C2=NN=C(O2)CC3=NC=C(C=C3)Cl)O)C4=C(C=CC=C4OC)OC