Cdc25s in Human Disease
The Cdc25s, and in particular Cdc25A and Cdc25B, are proto-oncogenes in humans and have been shown to be overexpressed in a number of cancers. The central role of Cdc25s in the cell cycle has garnered them considerable attention from the pharmaceutical industry as potential targets for novel chemotherapeutic (anti-cancer) agents. To date, no clinically-viable compounds targeting these enzymes have been described.
A large number of potent small-molecule Cdc25 Inhibitors have been identified that bind to the active site and belong to various chemical classes including natural products, lipophilic acids, quinonoids, electrophilies, sulfonylated aminothiazoles and phosphate bioisosteres. Although some progress has been made in developing potent and selective inhibitors for Cdc25 family of proteins, there is scope for development of novel therapeutic strategies to target them. A new class of peptide-derived inhibitors, based on sequence homology with the protein substrate, can be developed. It is challenging to use these compounds as drugs due to their lack of suitable ADME properties.
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