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Title: Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors

Abstract

The generation of selective inhibitors for specific protein kinases would provide new tools for analyzing signal transduction pathways and possibly new therapeutic agents. We have invented an approach to the development of selective protein kinase inhibitors based on the unexpected binding mode of 2,6,9-trisubstituted purines to the ATP binding site of human CDK2. The most potent inhibitor, purvalanol B (IC.sub.50 =6 nM), binds with a 30-fold greater affinity than the known CDK2 inhibitor, flavopiridol. The cellular effects of this class of compounds were examined and compared to those of flavopiridol by monitoring changes in mRNA expression levels for all genes in treated cells of Saccharomyces cerevisiae using high-density oligonucleotide probe arrays.

Inventors:
 [1]
  1. (Berkeley, CA), Schultz, Peter (Oakland, CA), Wodicka, Lisa (Santa Clara, CA), Meijer, Laurent (Roscoff, FR), Lockhart, David J. (Mountain View, CA)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
OSTI Identifier:
879568
Patent Number(s):
US 6573044
Application Number:
09/221406
Assignee:
The Regents of the University of California (Oakland, CA) LBNL
DOE Contract Number:  
AC03-76SF00098
Resource Type:
Patent
Country of Publication:
United States
Language:
English

Citation Formats

Gray, Nathanael S. Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors. United States: N. p., 2003. Web.
Gray, Nathanael S. Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors. United States.
Gray, Nathanael S. Tue . "Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors". United States. https://www.osti.gov/servlets/purl/879568.
@article{osti_879568,
title = {Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors},
author = {Gray, Nathanael S.},
abstractNote = {The generation of selective inhibitors for specific protein kinases would provide new tools for analyzing signal transduction pathways and possibly new therapeutic agents. We have invented an approach to the development of selective protein kinase inhibitors based on the unexpected binding mode of 2,6,9-trisubstituted purines to the ATP binding site of human CDK2. The most potent inhibitor, purvalanol B (IC.sub.50 =6 nM), binds with a 30-fold greater affinity than the known CDK2 inhibitor, flavopiridol. The cellular effects of this class of compounds were examined and compared to those of flavopiridol by monitoring changes in mRNA expression levels for all genes in treated cells of Saccharomyces cerevisiae using high-density oligonucleotide probe arrays.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Jun 03 00:00:00 EDT 2003},
month = {Tue Jun 03 00:00:00 EDT 2003}
}

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