883561-04-4

CA-224 is potent CDK4 inhibitor, is also a nonplanar analogue of fascaplysin that specifically inhibits Cdk4-cyclin D1 in vitro. CA-224 blocks the growth of cancer cells at G0/ G1 phase of the cell cycle. CA-224 also blocks the cell cycle at G2/M phase, which is explained by the fact that it inhibits tubulin polymerization. Additionally, CA-224 acts as an enhancer of depolymerization for taxol-stabilized tubulin. CA-224 selectively induces apoptosis of SV40 large Tantigen. transformed cells and significantly reduces colony formation efficiency, in a dose-dependent manner, of lung cancer cells. The promising efficacy of CA-224 in human xenograft models as well as its excellent therapeutic window indicates its potential for clinical development.