Fulacimstat is an orally available chymase inhibitor, with IC50s of 4, 3 nM for human and hamster chymase enzyme, respectively.
Fulacimstat inhibits human and hamster chymase enzyme with IC50s of 4 nM and 3 nM, respectively[1][2].
Isoprenaline induces cardiac fibrosis (24.4±1.8%) in hamsters, which is reduced dose dependently by Fulacimstat (16.4±1.2%, 12.4 ± 1.3%, 10.9±1.4% at 1, 3 and 10 mg/kg respectively) and by enalapril (17.7±1.5% at 20 mg/kg). Four weeks after MI, hamster hearts show an increased end diastolic pressure, and reduce contractility and relaxation. Compared to placebo (19.3±2 mmHg), Fulacimstat at 10 mg/kg reduce significantly the end diastolic pressure (13.2±1.4 mmHg) without any effects on blood pressure or heart rate. Moreover, treatment with Fulacimstat reduce the fibrotic area and improve the cardiac response to adrenergic stimulation[1].
References:
[1]. Hanna Tinel, et al. Abstract 13624: A Novel Chymase Inhibitor BAY 1142524 Reduces Fibrosis and Improves Cardiac Function After Myocardial Infarction in Hamster. Circulation. 2018;136:A13624.
[2]. Kanefendt F, et al. Pharmacokinetics, Safety, and Tolerability of the Novel Chymase Inhibitor BAY 1142524 in Healthy Male Volunteers. Clin Pharmacol Drug Dev. 2018 Jun 7.