VU0810464_product_DataBase

Bioactivity

VU0810464 is a potent and selective non-ureaG protein-gated inwardly-rectifying potassium channels (GIRK, Kir3) activator. VU0810464 displays nanomolar potency for neuronal (EC50=165 nM) and GIRK1/4 (EC50=720 nM) channels with improved brain penetration[1][2].

Target

EC50: 165 nM (GIRK 1/2); 720 nM (GIRK1/4 )

Invitro

VU0810464 (0, 0.1, 0.3, 1, 3, 10, 30 μM) produces a concentration‐dependent response curves of currents in SAN and HPC cells, in addition, VU0810464 is 9‐fold higher potency for Kir3 channel activation in neurons as compared to SAN cells[2].

In Vivo

VU0810464 (intraperitoneal injection; 30 mg/kg, 10 mg/kg; 30mg/kg; pre-treated 30 mins) produces a dose-dependent reduction of SIH response in Male C57BL/6J mice. To test if VU0810464 plays it role through Kir3 channel activation, VU0810464 (10 mg/kg) suppresses the SIH response in wild‐ type mice, but has no impact on Kcnj3−/− mice[2].VU0810464 (intraperitoneal injection ; 30 mg/kg; 15, 30, 45, or 60 min post‐injection) displays a favourable distribution to the brain (Kp,uu = 0.83), has a improvement over ML297 (Kp,uu= 0.32). Clearance of VU0810464 is rapid,brain and plasma half-lives is 20 min in a PK study[2]. Animal Model:

Name

VU0810464

CAS

2126040-21-7

Formula

C18H21ClFN3O

Molar Mass

349.83

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Vo BN, et al. VU0810464, a non-urea G protein-gated inwardly rectifying K+ (Kir 3/GIRK) channel activator, exhibits enhanced selectivity for neuronal Kir 3 channels and reduces stress-induced hyperthermia in mice.Br J Pharmacol. 2019 Jul;176(13):2238-2249 [2]. Wieting JM,et al. Discovery and Characterization of 1H-Pyrazol-5-yl-2-phenylacetamides as Novel, Non-Urea-Containing GIRK1/2 Potassium Channel Activators.ACS Chem Neurosci. 2017 Sep 20;8(9):1873-1879.

PeptideDB

VU0810464

CAS: 2126040-21-7 F: C18H21ClFN3O W: 349.83