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- W2471658052 abstract "Imatinib mesylate is a 2-phenylaminopyrimidine tyrosine kinase inhibitor with specific activity for ABL, platelet-derived growth factor receptor, and c-kit receptor. The pharmacological basis of this interaction has been elucidated by crystallographic studies. Imatinib mesylate binds to the amino acids of the BCR-ABL tyrosine kinase ATP binding site and stabilizes the inactive, non-ATP-binding form of BCR-ABL, thereby preventing tyrosine autophosphorylation, and in turn, phosphorylation of its substrates. This process ultimately results in a switch-off of the downstream signaling pathways that promote leukemogenesis. Despite high rates of hematologic and cytogenetic responses to imatinib therapy, the emergence of resistance to imatinib has been recognized as a major problem in the treatment of Ph-positive leukemia. Considerable progress has been made in developing therapeutic agents that are effective against molecular targets specifically expressed in CML cells. It is important to emphasize that BCR-ABL is the ideal target for therapy even at relapse; at least one general mechanism of resistance involves maintenance of an active BCR-ABL kinase inside leukemic cells. It is also notable that the high frequency of BCR-ABL mutations and amplifications represents the high degree of heterogeneity in patients with advanced CML, in whom multiple leukemic clones may exist. For these reasons, a single inhibitor is unlikely to be able to block all mutants described so far." @default.
- W2471658052 created "2016-07-22" @default.
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- W2471658052 date "2003-08-01" @default.
- W2471658052 modified "2023-09-23" @default.
- W2471658052 title "[Molecular-target therapy of Ph-positive leukemia by imatinib (tyrosine kinase inhibitor)]." @default.
- W2471658052 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12938259" @default.
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