title: Dasatinib.
abstract: Dasatinib, (former BMS 354825), is an orally available small-molecule multikinase inhibitor. It potently inhibits BCR-ABL and SRC-family kinases (SRC, LCK, YES, FYN), but also c-KIT, PDGFR-alpha and beta, and ephrin receptor kinase.Dasatinib is about 300 times more potent than imatinib in cells expressing unmutated BCR-ABL in vitro. The drug has demonstrated activity against clinically relevant mutations, including those associated with poor prognosis during ongoing imatinib therapy.Dasatinib is approved for the treatment of patients with BCR-ABL-positive chronic myeloid leukemia (CML), resistant or intolerant to imatinib in chronic, accelerated, and blast phase. It also is approved for the treatment of Philadelphia Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) resistant or intolerant to imatinib.A single daily dose of 100 mg in chronic phase CML results in high hematologic and molecular remission rates and prolongation of survival. In accelerated and blastic phase as well as in ALL, 70 mg twice daily is recommended. Complete hematologic and cytogenetic remissions (CR) frequently occur even in this patient group with poor prognosis. Remissions however are very short.Side effects of dasatinib are frequent but mostly moderate and manageable and include cytopenias and pleural effusions. The role of dasatinib in other diseases, including solid tumors, has to be identified.
authors.affiliation: Medizinische Klinik III, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunnen 20-26, Heilbronn, 74078, Germany. markus.lindauer@slk-kliniken.de
authors.forename: Markus
authors.initials: M
authors.lastname: Lindauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
mesh_terms: D002986:Clinical Trials as Topic; D000069439:Dasatinib; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D016374:Oncogene Proteins v-abl / Q000037:antagonists & inhibitors; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D016374:Oncogene Proteins v-abl; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D019061:src-Family Kinases; D000069439:Dasatinib