CCT129202

CCT129202 is a small molecule, ATP-competitive, pan-Aurora kinase inhibitor targeting Aurora A, Aurora B, and Aurora C with high potency (IC50 values of 0.042 μM, 0.198 μM, and 0.227 μM, respectively). It exhibits high selectivity for Aurora kinases over a panel of other kinases and induces cell cycle arrest at G2/M, resulting in abnormal spindle formation, chromosomal misalignment, and apoptosis in tumor cells. Mechanistically, CCT129202 inhibits the phosphorylation of histone H3 (Aurora B inhibition) and stabilizes p53 protein (Aurora A inhibition), leading to upregulation of p21 and downstream effects on the Rb/E2F pathway with reduced thymidine kinase 1 expression. In preclinical studies, CCT129202 significantly inhibited the growth of various human tumor xenografts and has been used in vivo with measurable pharmacodynamic effects. Development as an anticancer therapy has largely focused on solid tumors and hematological malignancies[1][2][4][6][7].