WNK-IN-11 D3

WNK-IN-11 D3 is an orally active, selective and potent With-No-Lysine (WNK) kinase inhibitor. WNK-IN-11 D3 is effective at regulating cardiovascular homeostasis[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> Ser/Thr Protease

Research Areas >> Cardiovascular Disease

WNK[1]

WNK-IN-11 D3 (1.5 mg/kg; p.o.) shows an improved rat PK profile, including lower clearance, improvement in absolute oral exposure, and a 2-fold improvement in oral bioavailability[1]. WNK-IN-11 D3 (30 mg/kg; p.o.) shows significant reductions in systolic blood pressure (SBP) vs untreated mice[1]. WNK-IN-11 D3 (0~100 mg/kg; p.o.) induces dose dependent diuresis, natriuresis, and kaliuresis, from 10 to 100 mg/kg[1]. WNK-IN-11 D3 shows trends toward reduction of blood pressure, stroke volume, and total peripheral resistance, while increasing heart rate. WNK-IN-11 D3 shows efficacy in rodent models of hypertension and volume overload[1]. Animal Model: Sprague−Dawley rats[1] Dosage: 1.5 mg/kg Administration: P.o. Result: Showed an improved rat PK profile, including lower clearance, improvement in absolute oral exposure, and a 2-fold improvement in oral bioavailability. Animal Model: FVB mice[1] Dosage: 30 mg/kg Administration: P.o. Result: Showed significant reductions in systolic blood pressure (SBP) vs untreated mice. Animal Model: FVB mice[1] Dosage: 0~100 mg/kg Administration: P.o. Result: Induced dose dependent diuresis, natriuresis, and kaliuresis, from 10 to 100 mg/kg.

[1]. Yamada K, Levell J, Yoon T, et al. Optimization of Allosteric With-No-Lysine (WNK) Kinase Inhibitors and Efficacy in Rodent Hypertension Models. J Med Chem. 2017;60(16):7099-7107.