VU591 hydrochloride

VU591 hydrochloride is a selective inhibitor of the renal outer medullary potassium channel (ROMK, Kir1.1). VU591 hydrochloride inhibits ROMK via binding to the intracellular pore region near residues Val168 and Asn171, with IC₅₀ of 240 nM in Tl⁺ flux assay and 300 nM in whole cell patch clamp electrophysiology, suppresses native ROMK mediated K⁺ secretion in isolated perfused rat collecting ducts, and exerts antidepressive effects in the mouse tail suspension test (TST). VU591 hydrochloride can be used for the study of ROMK channel function, renal potassium handling, antidepressant mechanisms, and diuretic drug discovery^{[1][2][3][4][5]}. IC50 & Target:IC50: 0.24 μM (ROMK)^[1]. In Vitro:VU591 (1 nM-30 μM; 5-10 min) hydrochloride inhibits rat ROMK1 (Kir1.1) with IC₅₀ of 240 nM in Tl⁺ flux assay and 300 nM in whole-cell patch-clamp electrophysiology^[1].
VU591 (10 μM; 4 10 min) hydrochloride produces 86% inhibition of human ROMK1 in patch clamp assay, and shows no significant inhibition of Kir7.1, Kir2.1, Kir2.3, Kir4.1, Kir6.2/SUR1, Slo1/β1, Kv1.3, or hERG channels^[1].
VU591 (1-10 μM; luminal perfusion) hydrochloride inhibits net K⁺ transport (J_K) from 7.0 to 3.6 pmol/min/mm in isolated perfused rat cortical collecting ducts, with no significant effect on Na⁺ transport^[1].
VU591 (300 nM) hydrochloride shows voltage-dependent "knock-off" at hyperpolarizing potentials, with block decreasing at strong negative voltages^[1].
VU591 (10 μM; 4 h dialysis) hydrochloride exhibits high plasma protein binding (human: 99.14%; rat: 98.39%) in rapid equilibrium dialysis assay^[1].
VU591 (15 min incubation) hydrochloride shows metabolic stability, with 60-80% compound remaining in human and rat liver microsomes^[1].
VU591 (up to 30 μM) hydrochloride inhibition of ROMK is abolished by mutation of pore residues Val168 and Asn171^[3].
VU591 (50 and 100 μM; 4-10 min) hydrochloride exhibits 6.8% and 22.6% inhibition for Kir2.1 D172N, and 9% and 28% inhibition for Kir2.1 C169V/D172N at corresponding concentrations^[3].
VU591 (20 μM; 20 min) hydrochloride blocks the cardioprotective effect of diazoxide in isolated mouse cardiomyocytes^[5]. In Vivo:VU591 (5 μL of 20 mM; i.c.v.; 30 min) hydrochloride decreases immobile time in the tail suspension test (TST), confirming ROMK involvement in antidepressant-like effects^[2].