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Leading researchers, from the Novartis group that pioneered
Gleevec/Gliveca"[ and around the world, comprehensively survey the
state of the art in the drug discovery processes (bio- and
chemoinformatics, structural biology, profiling, generation of
resistance, etc.) aimed at generating PTK inhibitors for the
treatment of various diseases, including cancer. Highlights include
a discussion of the rationale and the progress made towards
generating "selective" low molecular-weight kinase inhibitors; an
analysis of the normal function, role in disease, and application
of platelet-derived growth factor antagonists; and a summary of the
factors involved in successful structure-based drug design.
Additional chapters address the advantages and disadvantages of in
vivo preclinical models for testing protein kinase inhibitors with
antitumor activity and the utility of different methods in the drug
discovery and development process for determining "on-target" vs
"off-target" effects of kinase inhibitors.
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