CMPD101

CMPD101 (CAS No.: 865608-11-3) is a potent, selective, and membrane-permeable small-molecule inhibitor of G protein-coupled receptor kinases GRK2 and GRK3, key regulators of GPCR desensitization and signaling, widely studied in the context of cardiovascular and smooth muscle biology. It exhibits high inhibitory activity in the nanomolar range against GRK2 and GRK3, while demonstrating substantially weaker activity against related kinases such as GRK1 and GRK5, as well as off-target enzymes including ROCK2 and PKCα, indicating a favorable selectivity profile for dissecting GRK2/3-mediated pathways. Functionally, CMPD101 modulates GPCR signaling cascades, including enhancement of cAMP accumulation in β2-adrenergic receptor-expressing cell systems, and has been shown to influence smooth muscle contractility responses to multiple agonists in ex vivo tissue models. In cellular assays, it does not markedly interfere with agonist-induced ERK1/2 or Elk-1 phosphorylation at commonly used concentrations, although modest effects on basal signaling may be observed at higher exposure levels. This compound is widely utilized as a pharmacological tool in studies of GPCR regulation, cardiac dysfunction, and receptor desensitization mechanisms, with experimental concentrations typically selected based on specific assay conditions and biological endpoints.