VU0134992 is an Kir4.1 blocker with an IC50 value of 0.97 μM
VU0134992 inhibits Kir4.1 with an IC50 value of 0.97 μM and is 9-fold selective for homomeric Kir4.1 over Kir4.1/5.1 concatemeric channels (IC50 = 9 μM) at -120 mV.?In thallium (Tl+) flux assays, VU0134992 is greater than 30-fold selective for Kir4.1 over Kir1.1, Kir2.1, and Kir2.2;?is weakly active toward Kir2.3, Kir6.2/SUR1, and Kir7.1;?and is equally active toward Kir3.1/3.2, Kir3.1/3.4, and Kir4.2.
VU0134992 displayed a large free unbound fraction (fu) in rat plasma (fu = 0.213).?Consistent with the known role of Kir4.1 in renal function, oral dosing of VU0134992 led to a dose-dependent diuresis, natriuresis, and kaliuresis in rats.