application): Protein kinases play key roles in many cell signaling pathways, and enhanced activity of the protein kinases has been implicated in cancer and other proliferative diseases. Specific inhibitors would allow selective regulation of cell growth mechanisms and therefore, may be potentially useful cancer therapeutics. The overall goal of this project is to discover new classes of potent and specific inhibitors of individual serine/threonine and tyrosine protein kinases. The applicant proposes to approach this problem with a two-pronged combinatorial, transition state analog strategy to develop highly potent bisubstrate inhibitors.
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