title: Discovery of a novel protein kinase B inhibitor by structure-based virtual screening.
abstract: Protein kinase B (PKB/AKT) is a promising and attractive therapeutic target in anticancer drug development. Herein, we report the findings of virtual screening for novel ATP-competitive inhibitors of AKT-2 using 2D- and 3D-similarity searching and sequential molecular docking with two crystal structures of AKT-2. Our multistep approach led to the identification of a low micromolar AKT-2 inhibitor (IC(50)=1.5 microM) with a novel scaffold. The experimentally validated inhibitor represents the starting point for an optimization program.
authors: Torrey Pines Institute for Molecular Studies, Port St Lucie, FL 34987, USA. jmedina@tpims.org
authors: Jose L
authors: JL
authors: Medina-Franco
authors: Marc A
authors: MA
authors: Giulianotti
authors: Yongping
authors: Y
authors: Yu
authors: Liangliang
authors: L
authors: Shen
authors: Libo
authors: L
authors: Yao
authors: Narender
authors: N
authors: Singh
mesh_terms: D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D055808:Drug Discovery; D006801:Humans; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt