title: Structure-based design of potent CDK1 inhibitors derived from olomoucine.
abstract: Cyclin-dependent kinase 1 (CDK1), an enzyme participating in the regulation of the cell cycle, constitutes a possible target in the search for new antitumor agents. Starting from the purine derivative olomoucine and following a structure-based approach, potent inhibitors of this enzyme were rapidly identified. The molecular modeling aspects of this work are described.
authors.affiliation: Novartis Pharma Inc., Oncology Research Department, Basel, Switzerland. pascal.furet@pharma.novartis.com
authors.forename: P
authors.initials: P
authors.lastname: Furet
authors.forename: J
authors.initials: J
authors.lastname: Zimmermann
authors.forename: H G
authors.initials: HG
authors.lastname: Capraro
authors.forename: T
authors.initials: T
authors.lastname: Meyer
authors.forename: P
authors.initials: P
authors.lastname: Imbach
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D042846:CDC2-CDC28 Kinases; D017076:Computer-Aided Design; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007701:Kinetin; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D011687:Purines / Q000737:chemistry* / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
chemical_list: D004791:Enzyme Inhibitors; D011687:Purines; C090046:olomoucine; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D007701:Kinetin