Biological Activity
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].
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].
in vivo
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: | SpragueDawley 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.
|
References
[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.
