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

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

doi:10.1016/j.bmcl.2011.12.121

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

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

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

13 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 language	English
Pages (from-to)	1629-1632
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2011.12.121
State	Published - 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.

Funding

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.

Funders	Funder number
National Institutes of Health (NIH)	RC1MH088480
University of Kentucky
Kentucky Science and Engineering Foundation	KSEF-925-RDE-008

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2011.12.121

Cite this

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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.",

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AU - Zhan, Chang Guo

N1 - 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.

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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