Science Links Japan | Preclinical and clinical profile of imatinib mesilate, a potent protein-tyrosine kinase inhibitor for CML therapy.

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

Accession number;03A0151153

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

Author; TOGA WAKAKO (Nobarutisu Fama Tsukubaken) KONDO MIDORI (Nobarutisu Fama Rinshokaihatsubu) TOKORO AKIO (Nobarutisu Fama Rinshokaihatsubu)

Journal Title;Folia Pharmacologica Japonica

Journal Code:G0740A

ISSN:0015-5691

VOL.121;NO.2;PAGE.119-128(2003)

Figure&Table&Reference;FIG.5, TBL.1, REF.33

Pub. Country;Japan

Language;Japanese

Abstract;Imatinib 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. (author abst.)

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