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:
-
- (Berkeley, CA), Schultz, Peter (Oakland, CA), Wodicka, Lisa (Santa Clara, CA), Meijer, Laurent (Roscoff, FR), Lockhart, David J. (Mountain View, CA)
- Issue Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- OSTI Identifier:
- 879568
- Patent Number(s):
- 6573044
- Application Number:
- 09/221406
- Assignee:
- The Regents of the University of California (Oakland, CA)
- Patent Classifications (CPCs):
-
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07D - HETEROCYCLIC COMPOUNDS
- 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 = {2003},
month = {6}
}
Works referenced in this record:
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journal, September 1994
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- European Journal of Biochemistry, Vol. 224, Issue 2
Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors: Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds
journal, February 1997
- Havlíček, Libor; Hanuš, Jan; Veselý, Jaroslav
- Journal of Medicinal Chemistry, Vol. 40, Issue 4
DNA SEQUENCING: Massively Parallel Genomics
journal, July 1997
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- Science, Vol. 277, Issue 5324