Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors.

Cdc25 phosphatases have been considered as attractive drug targets for anticancer therapy due to the correlation of their overexpression with a wide variety of cancers. We have been able to identify 32 novel Cdc25 phosphatase inhibitors with micromolar activity by means of a structure-based de novo design method with the two known inhibitor scaffolds. Because the newly discovered inhibitors are structurally diverse and have desirable physicochemical properties as a drug candidate, they deserve further investigation as anticancer drugs. The differences in binding modes of the identified inhibitors in the active sites of Cdc25A and B are addressed in detail.