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Though the Abl tyrosine kinase inhibitor imatinib mesylate has improved the
treatment of Bcr-Abl-positive leukemia, resistance is often reported in patients
with advanced-stage disease. Although several Src inhibitors are more effective
than imatinib and simultaneously inhibit Lyn, whose overexpression is associated
with imatinib-resistance, these inhibitors are less specific than imatinib. We
have identified a specific dual Abl-Lyn inhibitor, NS-187 (elsewhere described
as CNS-9), which is 25-55 times more potent than imatinib in vitro. NS-187 is
also at least 10 times as effective as imatinib in suppressing the growth of
Bcr-Abl-bearing tumors, and markedly extends the survival of mice bearing such
tumors.
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