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Scientists at Ambit Biosciences have identified a group of drug candidates
that can overcome the resistance commonly encountered by the Gleevec family of
tyrosine kinase inhibitors.
For all the remarkable success of Gleevec, the Novartis drug that targets
the BCR-ABL oncoprotein in chronic myelogenous leukemia, patients often develop
resistance to the drug. That's because the target protein can acquire mutations
that reduce or block the binding of the drug to its target.
Using a novel kinase profiling technology, Ambit scientists have identified
a number of known drug molecules that are already in the clinic that appear
effective in inhibiting target proteins containing such mutations. This group
includes the targets of Gleevec as well as Iressa and Tarceva. "Screening
clinical compounds against drug-resistant, mutated kinases takes advantage of
the propensity of protein kinase inhibitors to hit multiple targets, and
provides potentially new uses for drugs and new treatment options for patients,"
the authors write in the Proceedings of the National Academy of Sciences.
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