Discovery of a novel protein kinase B inhibitor by structure-based virtual screening Article

Medina-Franco, JL, Giulianotti, MA, Yu, Y et al. (2009). Discovery of a novel protein kinase B inhibitor by structure-based virtual screening . BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 19(16), 4634-4638. 10.1016/j.bmcl.2009.06.078

cited authors

  • Medina-Franco, JL; Giulianotti, MA; Yu, Y; Shen, L; Yao, L; Singh, N

authors

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 (IC50 = 1.5 μM) with a novel scaffold. The experimentally validated inhibitor represents the starting point for an optimization program. © 2009 Elsevier Ltd. All rights reserved.

publication date

  • August 15, 2009

published in

Digital Object Identifier (DOI)

start page

  • 4634

end page

  • 4638

volume

  • 19

issue

  • 16