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

Hwangseo Park, Young Jae Bahn, Seong Eon Ryu

Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-ku, Seoul 143-747, Republic of Korea. hspark@sejong.ac.kr

Bioorganic & medicinal chemistry letters 2009 Aug 1

filter terms:

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.

Citation

Hwangseo Park, Young Jae Bahn, Seong Eon Ryu. Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors. Bioorganic & medicinal chemistry letters. 2009 Aug 1;19(15):4330-4