New inhibitor of 3-phosphoinositide dependent protein kinase-1 identified from virtual screening

Wenchao Yang, Mohamed Diwan M. AbdulHameed, Adel Hamza, Chang Guo Zhan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been recognized as a promising anticancer target. Thus, it is interesting to identify new inhibitors of PDK1 for anticancer drug discovery. Through a combined use of virtual screening and wet experimental activity assays, we have identified a new PDK1 inhibitor with IC50 = ∼200 nM. The anticancer activities of this compound have been confirmed by the anticancer activity assays using 60 cancer cell lines. The obtained new PDK1 inhibitor and its PDK1-inhibitor binding mode should be valuable in future de novo design of novel, more potent and selective PDK1 inhibitors for future development of anticancer therapeutics.

Original languageEnglish
Pages (from-to)1629-1632
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number4
DOIs
StatePublished - Feb 15 2012

Bibliographical note

Funding Information:
The research was supported in part by the NIH (Grant RC1MH088480 to Zhan), Kentucky Science & Engineering Foundation (Grant KSEF-925-RDE-008 to Zhan) and the Center for Computational Sciences (CCS) at University of Kentucky . The entire work was carried out in Zhan’s lab at University of Kentucky. Wenchao Yang worked in Zhan’s lab at University of Kentucky as an exchange graduate student (2005–2009) or a postdoctoral fellow (since January 2010) from Central China Normal University. The authors also acknowledge the Center for Computational Sciences (CCS) at University of Kentucky for supercomputing time on IBM X-series Cluster with 340 nodes or 1,360 processors and a Dell Supercomputer Cluster consisting of 388 nodes or 4,816 processors.

Keywords

  • Anticancer activity
  • Enzyme
  • Enzyme inhibitor
  • Inhibitor identification

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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