Fulacimstat

Fulacimstat is an orally available chymase inhibitor, with IC₅₀s of 4, 3 nM for human and hamster chymase enzyme, respectively. IC50 & Target: IC50: 4 nM (human chymase enzyme), 3 nM (hamster chymase enzyme)^[1][2]. In Vitro: Fulacimstat inhibits human and hamster chymase enzyme with IC₅₀s of 4 nM and 3 nM, respectively^[1][2]. In Vivo: 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].