Tyrosine kinase inhibitor as a therapeutic drug for chronic myelogenous leukemia and gastrointestinal stromal tumor.

  title={Tyrosine kinase inhibitor as a therapeutic drug for chronic myelogenous leukemia and gastrointestinal stromal tumor.},
  author={Motowo Nakajima and Wakako Toga},
  journal={Nihon yakurigaku zasshi. Folia pharmacologica Japonica},
  volume={122 6},
  • M. Nakajima, W. Toga
  • Published 1 December 2003
  • Biology, Chemistry
  • Nihon yakurigaku zasshi. Folia pharmacologica Japonica
The Philadelphia chromosome found in leukemia cells of chronic myelogenous leukemia (CML) patients is produced by translocation between chromosomes 9 and 22, resulting in expression of a chimera protein of Bcr and Abl kinase in the cytoplasm. Bcr-Abl kinase attracted oncology researchers as a molecular target for CML therapy, and a variety of small Abl kinase inhibitors were synthesized. STI571 (imatinib mesylate) was produced by modification of 2-phenylaminopyrimidine, a core structure of… 
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1Pharmaceutical Science Department, Faculty of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia, 2Pharmaceutical Practice Department, Faculty of Pharmacy, Princess Nourah


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STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed and demonstrates the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer.
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.
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.
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
It is found that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined and a strategy for identifying inhibitors of STI-571 resistance is suggested.
Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL.
It is reported that Ph1-positive ALL cells express unique abl-derived tyrosine kinases of 185 and 180 kilodaltons that are distinct from the bcr-abl-derived P210 protein of CML.
Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative.
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Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
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Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL).
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