Dual tyrosine kinase inhibitors in chronic myeloid leukemia.

摘要: The Bcr-Abl inhibitor imatinib mesylate induces complete hematologic and cytogenetic remissions in most newly diagnosed chronic myeloid leukemia (CML) patients, but relatively few of them achieve molecular remission. In addition, is much less effective advanced phase-CML as well Philadelphia-positive (Ph+) acute lymphoblastic (ALL), mainly due to the development drug resistance. challenge for future improve current clinical results with kinase inhibitors CML, developing strategies that can eradicate residual disease overcome or prevent 'Dual' Src Abl are an attractive class compounds, since (a) these molecules able bind stringent conformational requirements respect imatinib, therefore allowing efficient inhibition several, resistance-associated mutant forms Bcr-Abl; (b) kinases have been shown be involved Bcr-Abl-mediated leukemogenesis upregulated some patients resistant imatinib. Here, we review development, mode action preclinical early evaluation several novel dual inhibitors.