title: An Antitumor 2-Hydroxyarylidene-4-cyclopentene-1,3-Dione as a Protein Tyrosine Kinase Inhibitor: Interaction Between TX-1123 Derivatives and Src Kinase.
abstract: BACKGROUND
  Protein tyrosine kinases (PTKs) play major roles in signal transduction during cell proliferation and apoptosis. Tyrphostin AG17 was previously shown to be a potent tumor growth inhibitor, while AG17 induced apoptosis and inhibited activity of cyclin-dependent kinase 2. We herein describe the binding features of tyrphostin AG17 analogs, such as TX-1123, with Src kinase (Src-K).
  
  
  METHODS
  Structural data for Src-K were obtained from a protein data bank (ID=2SRC), and the molecular interactions between Src-K and TX-1123 derivatives were examined.
  
  
  RESULTS
  TX-1123 exihibited potent Src-K inhibitory activity (half maximal-inhibitory concentration=2.2 μM), and fit into the pocket of the Src-K molecule as well as c-AMP did.
  
  
  CONCLUSIONS
  The binding profiles of TX-1123 derivatives differed from each other, while their Src-K inhibitory activities were affected by their fit in the Src-K molecule.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science Graduate School, Suzuka, Japan kohkura@suzuka-u.ac.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ohkura
authors.affiliation: Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science Graduate School, Suzuka, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tatematsu
authors.affiliation: Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.affiliation: Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hori
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D001597:Benzylidene Compounds / Q000737:chemistry*; D001665:Binding Sites; D003517:Cyclopentanes / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C475851:2-hydroxyarylidene-4-cyclopentene-1,3-dione; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D003517:Cyclopentanes; D047428:Protein Kinase Inhibitors; D019061:src-Family Kinases
keywords: Protein kinase; TX-1123 derivatives; kinase inhibitor