1391737-01-1

1391737-01-1 structure

Name	VU0463271
Synonyms	N-Cyclopropyl-N-(4-methyl-1,3-thiazol-2-yl)-2-[(6-phenyl-3-pyridazinyl)sulfanyl]acetamide Acetamide, N-cyclopropyl-N-(4-methyl-2-thiazolyl)-2-[(6-phenyl-3-pyridazinyl)thio]-

Description	VU0463271 is a potent KCC2 antagonist, with an IC50 of 61 nM.
Related Catalog	Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel Research Areas >> Neurological Disease
Target	IC50: 61 nM (KCC2)[1].
In Vitro	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[1].
In Vivo	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[1].
References	[1]. Delpire E, et al. Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: development of a highly selective and more potent in vitro probe. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4532-5.