title: Docking of protein kinase B inhibitors: implications in the structure-based optimization of a novel scaffold.
abstract: Protein kinase B (PKB/AKT) is an attractive therapeutic target in anticancer drug development. We have recently identified by docking-based virtual screening a low micromolar AKT-2 inhibitor. Additionally, the virtual screening hit represents a novel AKT-2 inhibitor scaffold. In this work, we discuss a structure-based design strategy toward the optimization of this hit. Following this strategy and using a herein validated docking protocol, we conducted the design of novel compounds with expected improved activity over the parent compound. The newly designed molecules have high predicted affinity for AKT-2; are synthetically accessible and are contained within the kinase-relevant property space.
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: Israel
authors.initials: I
authors.lastname: Velázquez-Martínez
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Fabian
authors.initials: F
authors.lastname: López-Vallejo
authors.forename: Ping
authors.initials: P
authors.lastname: Jia
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yu
authors.forename: Marc A
authors.initials: MA
authors.lastname: Giulianotti
authors.forename: Jose L
authors.initials: JL
authors.lastname: Medina-Franco
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt