VU0463271 quarterhydrate is a potent KCC2 antagonist with an IC50 of 61 nM [1].

VU0463271 is a highly effective antagonist targeting the neuronal-specific potassium-chloride cotransporter 2 (KCC2), demonstrating significant potency with an IC50 value of 61 nM. It exhibits over 100-fold selectivity against the closely related Na-K-2Cl cotransporter 1 (NKCC1) and shows no activity across a wide range of G-protein coupled receptors (GPCRs), ion channels, and transporters. VU0463271 is also characterized by rapid clearance in vitro [1]. When applied to transected CNS preparations, VU0463271 significantly elevates the firing rates in the Drosophila CNS. Concentrations of 1 μM of VU0463271 notably increased the peak firing rate by 2.7- and 2.5-fold over the baseline for OR and rdl strains, respectively [2]. Furthermore, doses ranging from 10-100 nM led to an approximate 20% reduction in CNS firing frequency in a minority of the preparations [2].

VU0463271 exhibits moderate-to-high clearance (CL=57 mL/min/kg) in rats when administered intravenously at a dose of 1 mg/kg. Its low steady-state volume of distribution (Vss 0.4 L/kg), combined with its clearance rate, results in a relatively short half-life (t1/2) of 9 minutes in vivo [1].