title: Virtual docking approaches to protein kinase B inhibition.
abstract: We examined some in silico approaches to identify Akt (protein kinase B) inhibitors. Experimental validation of selected compounds was achieved using a fluorescence-based enzymatic assay and a substrate phosphorylation assay involving the protein GSK-3. We report on success and failure obtained by using several strategies including FlexX, GOLD, and CSCORE, where the 100-200 top-scoring compounds from a 50000-compound library were experimentally tested. This study led to the identification of low micromolar Akt1 inhibitors.
authors.affiliation: The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Martino
authors.initials: M
authors.lastname: Forino
authors.forename: Dawoon
authors.initials: D
authors.lastname: Jung
authors.forename: John B
authors.initials: JB
authors.lastname: Easton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry*; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry; D000071679:Glycogen Synthase Kinase 3 beta; D007191:Indazoles / Q000737:chemistry; D007546:Isoquinolines / Q000737:chemistry; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D007546:Isoquinolines; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D000255:Adenosine Triphosphate; D000071679:Glycogen Synthase Kinase 3 beta; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha