Biochem/physiol Actions

Reversible: no

Primary TargetRGS4

Cell permeable: yes

Target IC₅₀: 17 nM for RGS4 inhibition

General description

A cell-permeable, thiadiazolidinone based, thiol reactive compound that covalently binds to the regulator of G protein signaling 4 (RGS4) and irreversibly inhibits its activity (IC₅₀ = 17 nM). Exhibits high selectivity over RGS19 and RGS16 (IC₅₀ = 140 nM and 6 µM, respectively) and has negligible effects towards RGS7, RGS8, and papain IC₅₀ = 100, 70, and 100 µM, respectively). Displays ~300-fold greater selectivity over GSK-3beta (IC₅₀ = 5.4 µM). Shown to disrupt RGS4/Gαo interaction and reverse the Gαo-induced membrane translocation of GFP-tagged RGS4 in HEK293 cells (~3 µM). Enhances Gαq-dependent Ca2+ signaling activated by the M3 muscarinic receptor. Potentiates Gαi-dependent muscarinic bradycardia and reverses D2 antagonist raclopride-induced akinesia and bradykinesia in a murine model of the movement disorder in Parkinson′s disease.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Blazer, L.L., et al. 2015. ACS Chem. Neurosci.6, 311.r>Turner, E., et al. 2012. ACS Med. Chem. Lett..3, 146.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Standard Handling (A)