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The dual specificity CDC25 phosphatases dephosphorylate two inhibitory phospho-amino acids of cyclin-dependent kinases, a major family of cell cycle regulators. CDC25 inhibitors constitute new anti-mitotic agents with potential anticancer activity. While screening through a collection of natural products derived from marine organisms for CDC25A inhibitors, we purified and identified coscinosulfate 1, a sesquiterpene sulfate from the New Caledonian sponge Coscinoderma matthewsi, along with 4. The purified compound 1 displayed significant inhibitory activity towards CDC25A (IC(50): 3 microM).

Cyclin-dependent kinases (CDKs) are widely involved in regulating the cell division cycle. The discovery of numerous alterations of CDKs, cyclins, their regulators and their substrates in many human tumours has strongly stimulated the search for chemical inhibitors of CDKs. The potential use of these potent and selective kinase inhibitors in cancer therapy is presently under investigation. Recently a group from Glaxo Wellcome unexpectedly discovered a potential new application of these CDK inhibitors to prevent chemotherapy-induced alopecia. These cyto-protective properties might also be extended to other tissues damaged during chemotherapy.

Cancer chemotherapy is the object of many fundamental and clinical researches. The development in molecular techniques and structural studies at the molecular level have led to the discovery of key proteins involved in the regulation of cell proliferation. This opened perspectives to characterize new anticancer drugs in order to reduce the limitations found with conventional drugs such as the lack of selectivity for cancer cells and resistance phenomena. This review presents the anticancer drugs in clinical investigations that target molecules involved in the signal transduction impairment, the cell cycle deregulation and the differentiation with comments on their mechanisms of action.