Abstract
The ABL inhibitor imatinib is a highly effective therapy for patients with chronic myeloid leukemia. Relapses after an initial response have been observed in some patients, and mutations of the BCR-ABL gene are the most common mechanism driving these relapses. Alternative ABL inhibitors have been identified that inhibit most of the common BCR-ABL mutations, and one has entered clinical trials. The structural basis for these results has yielded significant insights into the mechanism of action of these compounds, mechanisms of resistance, and their ability to inhibit the BCR-ABL mutants. These studies demonstrate the importance and impact of conducting scientific studies as part of clinical trials.
MeSH terms
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Antineoplastic Agents / metabolism*
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Antineoplastic Agents / therapeutic use
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Benzamides
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Clinical Trials as Topic
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Drug Resistance, Neoplasm*
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Enzyme Inhibitors / metabolism*
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Enzyme Inhibitors / therapeutic use
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Fusion Proteins, bcr-abl / antagonists & inhibitors
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Fusion Proteins, bcr-abl / chemistry
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Fusion Proteins, bcr-abl / metabolism
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Humans
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Imatinib Mesylate
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Models, Molecular
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Piperazines / metabolism*
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Piperazines / therapeutic use
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Protein Conformation
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Pyrimidines / metabolism*
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Pyrimidines / therapeutic use
Substances
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Antineoplastic Agents
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Benzamides
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Enzyme Inhibitors
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Piperazines
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Pyrimidines
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Imatinib Mesylate
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Fusion Proteins, bcr-abl