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   Comb Chem  High Throughput Screen. 2005 Mar;8(2):181-95. _Related
Articles,_
(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=15777182&tool=ExternalSearch)
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High throughput screening for protein  kinase inhibitors.

Wesche H, Xiao SH, Young  SW.

Amgen San Francisco, 1120 Veterans Blvd, South San Francisco, CA  94080, USA.
[EMAIL PROTECTED]

The pivotal role of kinases in signal  transduction and cellular regulation
has lent them considerable appeal as  pharmacological targets across a broad
spectrum of pathologies. Since the  discovery that the v-Src oncogene encoded a
protein kinase in 1978, kinases have  remained a focus of research for
pharmaceutical laboratories and academic groups  alike. Many have
sought to develop
orally available low molecular weight  synthetic kinase modulators
(predominantly inhibitors) and thus capitalize on  the links between
aberrant regulation
and disease. This interest in kinases as  drug targets was fueled in recent
years by the success of several kinase  inhibitors in the clinic, primarily
Gleevec for the treatment of chronic  myelogenous leukemia and Iressa for the
treatment of advanced non-small cell  lung cancer. This review focuses on the
development of small molecule drugs,  most of them binding in or close
to the ATP
binding pocket. After some general  considerations regarding the selection of a
particular kinase for drug  discovery, we will discuss the encouraging
lessons learned from some of the  kinase inhibitors currently in
various stages of
development. The majority of  this review is dedicated to a detailed
description and discussion of the various  assay formats currently
being employed for
high throughput  screening.

PMID: 15777182 [PubMed - in process]


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