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VU0463271 quarterhydrate is a potent KCC2 antagonist, with an IC₅₀ of 61 nM.

VU0463271 is a potent antagonist of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC₅₀ of 61 nM and >100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters. It is also found rapidly cleared in vitro.
VU0463271 is applied to the transected CNS preparation and resulted in a significant increase in firing rates of the Drosophila CNS with 1 μM VU0463271 resulting in a peak firing rate that was a 2.7- and 2.5-fold increase over baseline firing rate for OR and rdl strains, respectively.
VU0463271 (10-100 nM) results in approximately 20% reduction of CNS firing frequency within a small percentage of preparations.

VU0463271 is found to be a moderate-to-high clearance compound in rat (CL=57 mL/min/kg) following intravenous administration (1 mg/kg); the low volume of distribution at steady state (Vss 0.4 L/kg), coupled with moderate-to-high clearance produce a relatively short t1/2 (9 min) in vivo.

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