Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.

@article{Druker2001EfficacyAS,
  title={Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.},
  author={Brian J. Druker and Moshe Talpaz and Debra Resta and Bin Peng and E Buchdunger and John M. Ford and Nicholas Lydon and Hagop M. Kantarjian and Renaud Capdeville and Sayuri Ohno-Jones and Charles L. Sawyers},
  journal={The New England journal of medicine},
  year={2001},
  volume={344 14},
  pages={
          1031-7
        }
}
BACKGROUND BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia (CML). Since tyrosine kinase activity is essential to the transforming function of BCR-ABL, an inhibitor of the kinase could be an effective treatment for CML. METHODS We conducted a phase 1, dose-escalating trial of STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR-ABL tyrosine kinase. STI571 was administered orally to 83 patients with CML in the chronic phase in whom… 
STI571: targeting BCR-ABL as therapy for CML.
TLDR
Investigation of STI571 into CML treatment algorithms will require long-term follow-up data from the ongoing phase II and III clinical studies, which are expected to demonstrate the crucial role of the bcr-abl tyrosine kinase in chronic myelogenous leukemia pathogenesis.
Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.
TLDR
The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL.
BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review.
TLDR
An overview about the current treatment of Ph+ CML patients with the TKIs and the obstacles to successful treatment with these drugs is presented.
Tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia: so far so good?
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Recent laboratory evidence suggests that the development of drug resistance is a possibility (via amplification of the bcr-abl fusion gene, overexpression of P-glycoprotein or binding of ST1571 to alpha1 acid glycoprotein) and that combination therapy including ST 1571 should be considered.
Tyrosine kinase inhibitor as a therapeutic drug for chronic myelogenous leukemia and gastrointestinal stromal tumor.
TLDR
STI571 showed significant efficacy in the clinical study with CML patients at all stages: chronic phase, accelerated phase, and blast crisis, and certain point mutations in the ATP binding site were found to be a cause of resistance to STI571 in both Bcr-Abl and c-Kit kinases.
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Compared with other pyrido[2,3-d]pyrimidine analogues studied, PD166326 was the most potent inhibitor of Bcr-Abl-dependent cell growth and PD173955 inhibited kit ligand-dependent c-kit autophosphorylation and had a lesser effect on interleukin 3-dependent or granulocyte macrophage colony-stimulating factor-induced cell growth.
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TLDR
The various kinases inhibited by imatinib, nilotinib and dasatinib are reviewed, and the potential impact of kinase inhibition on the efficacy and safety of each agent is described.
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c-Kit Receptor Tyrosine Kinases Characterization of Potent Inhibitors of the Bcr-Abl and the Updated
The early stage of chronic myelogenous leukemia (CML) is caused by the tyrosine kinase Bcr-Abl. Imatinib mesylate (also known as STI-571 and Gleevec), a tyrosine kinase inhibitor, has shown
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Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.
TLDR
The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL.
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TLDR
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