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

Jose L. Medina-Franco, Marc A. Giulianotti, Yongping Yu, Liangliang Shen, Libo Yao, Narender Singh

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4634-4638
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number16
DOIs
StatePublished - Aug 15 2009
Externally publishedYes

Bibliographical note

Funding Information:
The authors are grateful to Dr. Colette Dooley for the valuable comments. The authors also wish to thank Kyle Kryak for his assistance. This work was supported by the State of Florida, Executive Office of the Governor’s Office of Tourism, Trade, and Economic Development. Yongping Yu thanks the National Nature Science Foundation of China (30772652). The authors thank OpenEye Scientific Software, Inc., for providing FRED, Fred-Receptor, omega and rocs programs.

Keywords

  • AKT
  • Cancer
  • Docking
  • Molecular similarity

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