[Chemical inhibitors of cyclic-dependent kinases: preclinical and clinical study]

In the past decade, the use of a large variety of cellular models and cell biology, biochemistry and molecular biology techniques has led to the discovery of key proteins that are intimately involved in the regulation of tumor growth. In particular, it has been shown that cyclin-dependent kinases (CDKs) are key regulators of the cell-division cycle. Their frequent deregulation in human tumors make them attractive targets for the identification of new antineoplasic agents. Intensive screening has led in the past few years to the identification of a series of selective and potent chemical inhibitors of CDKs. Drugs representing new lead structures like flavopiridol, indirubin and staurosporine++ derivatives have already been used in clinical evaluation for cancer treatment (clinical trials, phase I and II). Anticancer drug development is being pursued to reduce their toxic side effects, to improve their pharmacokinetic properties and to increase their anti-tumor activity. In this context, traditional drug screening methods in biological test systems have led to the discovery of new compounds such as purine derivatives and paullones, which display remarkable selectivity and efficiency. These novels drugs may result in substantial progress in cancer treatment in the near future.