Is Cdc25 a druggable target?

Abstract

Proper control of cell cycle progression requires the functionality of a small family of activating phosphatases termed Cdc25, which have been implicated in cancer and Alzheimer's disease. These protein tyrosine phosphatases are therefore recognized as attractive molecular targets for small molecules. We review the rationale, approaches, progress and challenges for developing small molecule inhibitors of the Cdc25 family. A number of potential chemical probes are discussed and their characteristics are summarized.

Fig. (1)

Potential druggable targets for Cdc25. The expression levels and activity of this phosphatase family are regulated by at least seven distinct mechanisms.

Fig. (2)

A detailed view of the catalytic core of Cdc25B. In the right panel a sulfate moiety is seen bound in the catalytic site.

Fig. (3)

Structural classification of known inhibitors of Cdc25 phosphatases.

Fig. (3)

Structural classification of known inhibitors of Cdc25 phosphatases.