Docking of protein kinase B inhibitors: implications in the structure-based optimization of a novel scaffold Article

Hernández-Campos, A, Velázquez-Martínez, I, Castillo, R et al. (2010). Docking of protein kinase B inhibitors: implications in the structure-based optimization of a novel scaffold . 76(3), 269-276. 10.1111/j.1747-0285.2010.01002.x

cited authors

  • Hernández-Campos, A; Velázquez-Martínez, I; Castillo, R; López-Vallejo, F; Jia, P; Yu, Y; Giulianotti, MA; Medina-Franco, JL

authors

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. © 2010 John Wiley & Sons A/S.

publication date

  • September 1, 2010

Digital Object Identifier (DOI)

start page

  • 269

end page

  • 276

volume

  • 76

issue

  • 3