(S)-PHA-533533

(S)-PHA-533533 is an inhibitor of cyclin-dependent kinase 2 (Cdk2)/cyclin A, Cdk2/cyclin E, Cdk5/p25, and Cdk1/cyclin B complexes and glycogen synthase kinase 3beta (GSK3beta, IC50s = 37, 55, 65, 208, and 732 nM, respectively, in cell-free assays). It selectively inhibits these complexes and GSK3beta over the Cdk4/cyclin D1 complex and a panel of 29 other kinases at 10 µM. (S)-PHA-533533 inhibits the growth of A2780 ovarian, HT-29 human colon, and HCT116 colorectal cancer cells (IC50s = 744, 639, and 1,354 nM, respectively) and induces cell cycle arrest at the G0/G1 phase in HT-29 cells. It reduces tumor growth in an A2780 mouse xenograft model when administered at a dose of 7.5 mg/kg. (S)-PHA-533533 also restores the expression of paternal UBE3A mRNA in a mouse model of Angelman syndrome.. SMILES: O=C(CCC1)N1C2=CC=C([C@@H](C(NC3=NNC(C4CC4)=C3)=O)C)C=C2. InChi Code: InChI=1S/C19H22N4O2/c1-12(19(25)20-17-11-16(21-22-17)14-4-5-14)13-6-8-15(9-7-13)23-10-2-3-18(23)24/h6-9,11-12,14H,2-5,10H2,1H3,(H2,20,21,22,25)/t12-/m0/s1. InChi Key: UAOIPNOTWOYAMU-LBPRGKRZSA-N