883050-24-6

CCG-50014 is an inhibitor of regulator of G protein signaling 4 (RGS4) (IC₅₀ = 30 nM) and is > 20-fold selective for RGS4 over other RGS proteins. RGS proteins bind to the Gα subunits of activated heterotrimeric G proteins and accelerate the rate of GTP hydrolysis, acting as GTPase-activating proteins. CCG-50014 irreversibly binds and destabilizes RGS4 with no effect on Gα₀, while blocking GTPase activity and Gα₀-dependent translocation of RGS4 to the membrane.

CCG-50014 is the most potent against the regulator of G-protein signaling protein type 4 (RGS4) (IC50 =30 nM) and is >20-fold selective for RGS4 over other RGS proteins. CCG-50014 binds covalently to the RGS, forming an adduct on two cysteine residues located in an allosteric regulatory site[1]. CCG50014, reduces nociceptive responses and enhances opioid-mediated analgesic effects in the mouse formalin test[2].

RGS4: 30 nM (IC₅₀); RGS8: 11 μM (IC₅₀); RGS16: 3.5 μM (IC₅₀); RGS19: 0.12 μM (IC₅₀)

[1] Blazer LL, et al. A nanomolar-potency small molecule inhibitor of regulator of G-protein signaling proteins. Biochemistry. 2011 Apr 19;50(15):3181-92. DOI:10.1021/bi1019622
[2] Yoon SY, et al. Intrathecal RGS4 inhibitor, CCG50014, reduces nociceptive responses and enhances opioid-mediated analgesic effects in the mouse formalin test. Anesth Analg. 2015 Mar;120(3):671-7. DOI:10.1213/ANE.0000000000000607