title: Identification of death-associated protein kinases inhibitors using structure-based virtual screening.
abstract: Death-associated protein kinases (DAPKs) function in the early stages of eukaryotic programmed cell death. DAPKs are now emerging as targets for drug discovery in novel therapeutic approaches for ischemic diseases in the brain, heart, kidney, and other organs. Using a structure-based virtual screening approach, we discovered potent and selective DAPKs inhibitors. 6 was found to be the most potent inhibitor with enzyme selectivity (IC(50) = 69 nM for DAPK1).
authors.affiliation: Drug Discovery Department, Research and Development Division, PharmaDesign, Inc., 2-19-8 Hatchobori, Chuo-ku, Tokyo 104-0032, Japan. okamoto@pharmadesign.co.jp
authors.forename: Masako
authors.initials: M
authors.lastname: Okamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takayama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishida
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Furuya
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018360:Crystallography, X-Ray; D064550:Death-Associated Protein Kinases; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014584:User-Computer Interface
chemical_list: D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D047428:Protein Kinase Inhibitors; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases