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Journal Article
Research Support, U.S. Gov't, P.H.S.
Review
Structure-based design of novel anti-cancer agents targeting aurora kinases.
Current Medicinal Chemistry. Anti-cancer Agents 2003 January
Aurora kinases are a family of mitotic serine-threonine kinases (S/T kinases), that functions as a class of novel oncogenes and are over-expressed in several solid tumors including breast, ovary, prostate, pancreas and colorectal cancer. To validate human ARK1 (Aurora2, STK15, HsAIRK1) as a drugable target in pancreatic cancer, we undertook a structure-based approach to design specific inhibitors utilizing homology modeling, affinity docking and an in vitro kinase assay in an iterative process. In this review, we discuss the biology, rationale for targeting and approaches taken to inhibit this family of protein kinases, implicated in dysregulated chromosome segregation and cytokinesis.
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