Identification of cylin-dependent kinase 1 inhibitors of a new chemical type by structure-based design and database searching |
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Authors: | Pascal Furet Thomas Meyer Peer Mittl Heinz Fretz |
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Affiliation: | (1) Oncology Research Department, Novartis Pharma Inc., CH-4002 Basel, Switzerland |
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Abstract: | We have selected cyclin-dependent kinase 1 (CDK1), an enzyme participating in the regulation of the cell cycle, as a target in our efforts to discover new antitumor agents. By exploiting available structural information, we designed an ATP-site directed ligand scaffold that allowed us to identify 4-(3-methyl-1,4-dioxo-1,4-dihydro-naphthalen-2-ylamino)-benzenesulfonamide as a new potent inhibitor of CDK1 in a subsequent database search. The synthesis and testing of some analogues confirmed the interest of this class of compounds as novel CDK1 inhibitors. |
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Keywords: | CDK1 cyclin-dependent kinase database search inhibitor structure-based design |
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