Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors

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

Full Record
Other Related Research

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:

Gray, Nathanael S. ^[1]

(Berkeley, CA), Schultz, Peter (Oakland, CA), Wodicka, Lisa (Santa Clara, CA), Meijer, Laurent (Roscoff, FR), Lockhart, David J. (Mountain View, CA)

Issue Date:: 2003-06-03

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) 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.

Copy to clipboard


                    Gray, Nathanael S. Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors.  United States.

Copy to clipboard


                    Gray, Nathanael S. Tue .  
        "Methods Of Using Chemical Libraries To Search For New Kinase Inhibitors".  United States.  https://www.osti.gov/servlets/purl/879568.

Copy to clipboard


                    
@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}

}

Copy to clipboard

Patent:

View Patent

Save / Share:

Export Metadata

Save to My Library

Similar records in DOE Patents and OSTI.GOV collections:

Method for distinguishing normal and transformed cells using G1 kinase inhibitors

Patent Crissman, Harry A. (Los Alamos, NM); Gadbois, Donna M. (Los Alamos, NM); Tobey, Robert A. (Los Alamos, NM); ...

A G.sub.1 phase kinase inhibitor is applied in a low concentration to a population of normal and transformed mammalian cells. The concentration of G.sub.1 phase kinase inhibitor is selected to reversibly arrest normal mammalian cells in the G.sub.1 cell cycle without arresting growth of transformed cells. The transformed cells may then be selectively identified and/or cloned for research or diagnostic purposes. The transformed cells may also be selectively killed by therapeutic agents that do not affect normal cells in the G.sub.1 phase, suggesting that such G.sub.1 phase kinase inhibitors may form an effective adjuvant for use with chemotherapeutic agents inmore »« less
Full Text Available
Chemical deposition methods using supercritical fluid solutions

Patent Sievers, Robert E. (Boulder, CO); Hansen, Brian N. (Boulder, CO)

A method for depositing a film of a desired material on a substrate comprises dissolving at least one reagent in a supercritical fluid comprising at least one solvent. Either the reagent is capable of reacting with or is a precursor of a compound capable of reacting with the solvent to form the desired product, or at least one additional reagent is included in the supercritical solution and is capable of reacting with or is a precursor of a compound capable of reacting with the first reagent or with a compound derived from the first reagent to form the desired material.more »« less
Full Text Available
Chemical inducible promoter used to obtain transgenic plants with a silent marker and organisms and cells and methods of using same for screening for mutations

Patent Zuo, Jianru [New York, NY]; Chua, Nam-Hai [Scarsdale, NY]

Disclosed is a chemically inducible promoter for transforming plants or plant cells with genes which are regulatable by adding the plants or cells to a medium containing an inducer or by removing them from such medium. The promoter is inducible by a glucocorticoid, estrogen or inducer not endogenous to plants. Such promoters may be used with any plant genes that can promote shoot regeneration and development to induce shoot formation in the presence of a glucocorticoid, estrogen or inducer. The promoter may be used with antibiotic or herbicide resistance genes or other genes which are regulatable by the presence ormore »« less
Full Text Available
Inhibitors of glycogen synthase 3 kinase

Patent Schultz, Peter (Oakland, CA); Ring, David B. (Palo Alto, CA); Harrison, Stephen D. (Berkeley, CA); ...

Compounds of formula 1: ##STR1## wherein R.sub.1 is alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, substituted with 0-3 substituents selected from lower alkyl, halo, hydroxy, lower alkoxy, amino, lower alkyl-amino, and nitro; R.sub.2 is hydroxy, amino, or lower alkoxy; R.sub.3 is H, lower alkyl, lower acyl, lower alkoxy-acyl, or amnino-acyl; R.sub.4 is H or lower alkyl; and pharmaceutically acceptable salts and esters thereof; are effective inhibitors of GSK3.
Full Text Available
Inhibitors of glycogen synthase 3 kinase

Patent Schultz, Peter; Ring, David B.; Harrison, Stephen D.; ...

Compounds of formula 1: ##STR00001## wherein R.sub.1 is alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, substituted with 0 3 substituents selected from lower alkyl, halo, hydroxy, lower alkoxy, amino, lower alkyl-amino, and nitro; R.sub.2 is hydroxy, amino, or lower alkoxy; R.sub.3 is H, lower alkyl, lower acyl, lower alkoxy-acyl, or amino-acyl; R.sub.4 is H or lower alkyl; and pharmaceutically acceptable salts and esters thereof; are effective inhibitors of GSK3.
Full Text Available

Similar Records