title: Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors.
abstract: 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.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-ku, Seoul 143-747, Republic of Korea. hspark@sejong.ac.kr
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Bahn
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D020687:cdc25 Phosphatases / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D020687:cdc25 Phosphatases