title: [Novel inhibitors of Bcr-Abl].
abstract: STI571 (imatinib; Gleevec) was developed to specifically target the tyrosine kinase activity of the Bcr-Abl protein in Philadelphia chromosome-positive chronic myeloid leukemia (CML). It also inhibits the activity of c-Kit and PDGFR. It is the first-line drug for newly diagnosed CML, with remarkable efficacy to patients in the chronic phase of this cancer. However, CML patients in the accelerated phase or blast crisis often relapse due to drug resistance. STI571 fails to eradicate leukemic stem cells, and BCR-ABL(+). cells remain detectable in the majority of patients. The necessity for alternative or additional treatment for STI571-resistant leukemia resulted in the development of a second generation of drugs for targeted therapies. In this review a literature overview of the alternative inhibitors which were designed to override STI571 resistance and decrease the aberrant kinase activity of Bcr-Abl protein with higher efficiency is presented.
authors.affiliation: Zakład Biologii Molekularnej Nowotworów Uniwersytetu Medycznego w Łodzi.
authors.forename: Justyna
authors.initials: J
authors.lastname: Jakubowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Czyz
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids; D000068877:Imatinib Mesylate; D007211:Indoles; D020128:Inhibitory Concentration 50; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009154:Mutation; D000077767:Panobinostat; D010879:Piperazines; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines; D011728:Pyridones; D011743:Pyrimidines; D013844:Thiazoles
chemical_list: C493107:AP23464; D000970:Antineoplastic Agents; D001549:Benzamides; D006877:Hydroxamic Acids; D007211:Indoles; C473352:PD 166326; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011728:Pyridones; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000255:Adenosine Triphosphate; D000077767:Panobinostat; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; C506918:bafetinib; D000069439:Dasatinib; C410732:PD 180970