Uses
CMPD101 hydrochloride is a novel membrane-permeable, small-molecule inhibitor of both GRK2 and GRK3 with IC50s of 18 nM and 5.4 nM, respectively. CMPD101 hydrochloride also inhibits Rho-associated kinase 2 (ROCK-2) and PKCα (IC50s =1.4 μM and 8.1 μM, respectively)[1].
Biological Activity
CMPD101 is an active site-targetingpotent and subtype-selective G protein-coupled receptor kinase GRK2 & GRK3 inhibitor (human GRK2/3 IC50 = 54/32 nM with 3 μM ATP and tubulin dimer as substrate; bovine GRK2 IC50 = 290 nM with 0.5 mM ATP and bROS as substrate; no GRK1/5 inhibition at 125 μM). CMPD101 selectively inhibits GPR39 agonist-induced β-arrestin recruitment (by 94% at 10 μM against 30 μM GPR39-C3/50 μM ZnCl2)but not cAMP pathway desensitization in cultures and prevents β-arrestin2-biased D2R ligand UNC9994(1 μg/side bilateral local injection) from blocking NMDAR antagonist PCP (6 mg/kg i.p.)-induced locomotion (60%/12% blockage without/with 0.5 μg CMPD101 co-injection) in mice in vivo.
