Cyclin-dependent kinase 1 (Cdk1) complexes with different cyclins, with the cyclin determining substrate specificity. Ro 3306 is a cell-permeable, reversible inhibitor of Cdk1, showing preference for Cdk1/cyclin B1 (Ki = 35 nM) over Cdk1/cyclin A (Ki = 110 nM), two CDK complexes which regulate cell cycling. It also inhibits Cdk2 (Ki = 340 nM), PKCδ (Ki = 318 nM), and serum- and glucocorticoid-induce kinase (Ki = 497 nM) but not Cdk4. Through its effects on Cdk1, Ro 3306 reversibly arrests proliferating cells at the G2/M phase border, allowing cell synchronization without the use of microtubule poisons. Prolonged treatment of cells with Ro 3306 induces apoptosis and this can be augmented in acute myeloid leukemia cells by stimulating p53 activity with nutlin-3.
