Imarikiren

Imarikiren (AK-272 free base) is an orally active, selective Renin inhibitor with an IC₅₀ value of 2.1 nM against h-Renin. Imarikiren blocks the conversion of Angiotensinogen to Angiotensin I and reduces mean arterial pressure by inhibiting Angiotensin II that binds to AT1. Imarikiren alleviates myocardial hypertrophy and pulmonary congestion, exerting cardioprotective effects. Imarikiren can be used in research related to hypertension and heart failure^[1][2][3]. In Vitro:Imarikiren potently inhibits endogenous plasma renin with an IC₅₀ of 2.1 nM; it exhibits no significant inhibitory activity against pepsin or cathepsin D even at concentrations as high as 10 μM^[1].
Imarikiren (0.5 nM-500 mM) potently inhibits plasma renin (with an IC₅₀ of 2.1 nM) and mouse plasma renin (with an IC₅₀ of 53 nM) in vitro^[2]. In Vivo:Imarikiren (TAK-272) (3-10 mg/kg; p.o.; single dose) exerts potent, dose-dependent, long-lasting antihypertensive efficacy in dTg rats, with the 3 mg/kg oral dose matching and the 10 mg/kg oral dose exceeding the efficacy of 75 mg/kg aliskiren at key time points^[1].
Imarikiren (30-300 mg/kg; p.o.; once daily; 36 days) prolongs survival in CSQ-tg heart failure mice in a dose-dependent manner, with the 300 mg/kg dose producing a statistically significant survival benefit^[2].
Imarikiren (30-300 mg/kg; p.o.; once daily; 12-13 days, 16-17 days, or 19 days) at 300 mg/kg reduces cardiac hypertrophy, lung congestion, and plasma heart failure biomarkers, inhibits left ventricular systolic dysfunction, and reduces cardiomyocyte injury in CSQ-tg heart failure mice, while 100 mg/kg reduces lung congestion^[2].
Imarikiren (300 mg/kg; p.o.) potently inhibits plasma renin activity in CSQ-tg heart failure mice without reducing systolic blood pressure^[2].