SPH3127

SPH3127 (DRI 18) is a novel, highly potent, and orally active direct renin inhibitor (recombinant human-renin IC50=0.4 nM, human plasma renin activity IC50=0.45 nM). SPH3127 shows antihypertensive effect and can be used in essential hypertension research[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Renin

SPH3127 (oral administration; 0-10 mg/kg; once) shows favorable bioavailability in cynomolgus monkeys[1]. SPH3127 (oral administration; 0-3 mg/kg; once) shows a hypotensive effect on tsukuba hypertensive mice[1]. Animal Model: Cynomolgus monkeys pretreated with a low-sodium diet and furosemide[1] Dosage: 0, 1, 3, and 10 mg/kg Administration: Oral administration; 1, 3, and 10 mg/kg; once Result: Inhibited plasma renin activity with the IC50 value of 0.46 nM, and showed hypotensive effect. Animal Model: Tsukuba hypertensive mice (THM)[1] Dosage: 0, 0.3, 1, or 3 mg/kg Administration: Oral administration; 0, 0.3, 1, or 3 mg/kg; once Result: Exhibited a hypotensive effect on tsukuba hypertensive mice in a dose-dependent manner from 0.3 to 3 mg/kg, and showed a maximum hypotensive effect of approximately 30 mmHg at 2-3 h after administration at any dose.

[1]. Daisuke Iijima, et al. Discovery of SPH3127: A Novel, Highly Potent, and Orally Active Direct Renin Inhibitor. J Med Chem. 2022 Aug 8.