title: Structure-based design of novel anti-cancer agents targeting aurora kinases.
abstract: 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.
authors.affiliation: Arizona Cancer Center, Division of Hematology/Oncology and Division of Medicinal Chemistry, University of Arizona, 1515, N. Campbell Avenue, Tucson, AZ 85724, USA. dmahadevan@azcc.arizona.edu
authors.forename: Daruka
authors.initials: D
authors.lastname: Mahadevan
authors.forename: David J
authors.initials: DJ
authors.lastname: Bearss
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Vankayalapati
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases