VU 0463271

Research use only, not for human use.

VU 0463271 is a potent, selecitve inhibitor of the neuronal K-Cl cotransporter KCC2 with IC50 of 61 nM.

VU 0463271 is a potent, selecitve inhibitor of the neuronal K-Cl cotransporter KCC2 with IC50 of 61 nM; displays >100-fold selectivity versus NKCC1 (>100 uM), no significant activities on a panel of 68 GPCRs, ion channels and transporters; exhibts 9-times more potent than ML077, and maintains an excellent ancillary pharmacology profile.

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.

VU0463271

Membrane Transporter/Ion Channel

Chloride Channel

Chloride Channel

——

——

1391737-01-1

382.5

C19H18N4OS2

>98% (HPLC)

In Vitro:?DMSO : 25 mg/mL (65.36 mM)

O=C(N(C1CC1)C2=NC(C)=CS2)CSC3=NN=C(C4=CC=CC=C4)C=C3

N-Cyclopropyl-N-(4-methyl-2-thiazolyl)-2-[(6-phenyl-3-pyridazinyl)thio]acetamide

(-20℃)

With Ice Pack

≥ 2 years