CCT251545 is an orally bioavailable inhibitor of Wnt signaling (IC50 = 5 nM). It is a potent and selective inhibitor of the human mediator complex-associated protein kinases Cdk8 and Cdk19. Through its effects on Cdk8 and Cdk19, CCT251545 alters Wnt pathway-regulated gene expression. It reduces tumor growth in COLO 205 human colon cancer xenografts after oral dosing (70 mg/kg bid) and in Wnt-dependent tumors.
CCT251545 is a potent inhibitor of WNT signaling with good oral pharmacokinetics.
ChEBI: CCT251545 is a chloropyridine that is 3-chloropyridine substituted by a 1-oxo-2,8-diazaspiro[4.5]decan-8-yl group and a 4-(1-methyl-1H-pyrazol-4-yl)phenyl group at positions 4 and 5, respectively. It is an orally bioavailable inhibitor of Wnt signaling (IC50 = 5 nM) and a potent and selective chemical probe for cyclin-dependent kinases CDK8 and CDK19. It has a role as a Wnt signalling inhibitor, an antineoplastic agent and an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor. It is a chloropyridine, a member of pyrazoles and an azaspiro compound.
[1]. mallinger a, crumpler s, pichowicz m, et al. discovery of potent, orally bioavailable, small-molecule inhibitors of wnt signaling from a cell-based pathway screen. j med chem, 2015, 58(4): 1717-1735.
[2]. dale t, clarke pa, esdar c, et al. a selective chemical probe for exploring the role of cdk8 and cdk19 in human disease. nat chem biol, 2015, 11(12): 973-980.
