• Nippon Yakurigaku Zasshi · Feb 2003

    Review

    [Preclinical and clinical profile of imatinib mesilate, a potent protein-tyrosine kinase inhibitor for CML therapy].

    • Wakako Toga, Midori Kondo, and Akio Tokoro.
    • Preclinical Development Divisions, Tsukuba Research Institute, Novartis Pharma K.K., Ohkubo 8, Tsukuba 300-2611, Japan. wakako.toga@pharma.novartis.com
    • Nippon Yakurigaku Zasshi. 2003 Feb 1; 121 (2): 119-28.

    AbstractImatinib mesilate (Glivec) is a protein-tyrosine kinase inhibitor that potently inhibits the Bcr-Abl tyrosine kinase as well as the receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, at in vitro and cellular kinase assay levels. Since Bcr-Abl tyrosine kinase plays a key role in chronic myelogenous leukemia (CML) patients, treatment with imatinib mesilate that potently inhibits Bcr-Abl tyrosine kinase could be a promising therapeutic approach to CML. Imatinib mesilate was shown to inhibit proliferation of bcr-abl-positive cell lines and suppress the formation of bcr-abl-positive colonies in cells derived from bone marrow of CML patients. This compound induced apoptosis in a variety of bcr-abl-positive cells. Moreover, in vivo data indicated that imatinib mesilate suppress growth and formation of bcr-abl-positive tumors in mice. As the profile expected from the preclinical studies, imatinib mesilate showed impressive hematological and cytogenic responses in the clinical trials, including interferon-alpha-resistant or intolerant patients.

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