title: [Preclinical and clinical profile of imatinib mesilate, a potent protein-tyrosine kinase inhibitor for CML therapy].
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.
authors.affiliation: Preclinical Development Divisions, Tsukuba Research Institute, Novartis Pharma K.K., Ohkubo 8, Tsukuba 300-2611, Japan. wakako.toga@pharma.novartis.com
authors.forename: Wakako
authors.initials: W
authors.lastname: Toga
authors.forename: Midori
authors.initials: M
authors.lastname: Kondo
authors.forename: Akio
authors.initials: A
authors.lastname: Tokoro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D002455:Cell Division / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl