Dasatinib.
Dasatinib is an orally bioavailable potent inhibitor of multiple tyrosine kinases, including ABL and SRC. Preclinical studies have shown dasatinib to be a much more potent inhibitor of BCR-ABL than imatinib is, and to harbor efficacy against nearly all imatinib-resistant BCR-ABL mutants. Phase I clinical studies have been conducted in imatinib-resistant and -intolerant chronic myeloid leukemia and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. No dose-limiting toxicity was observed at doses that harbored substantial clinical efficacy. Multinational phase II studies have confirmed the phase I experience and have led to accelerated approval by the U.S. Food and Drug Administration for the treatment of imatinib-resistant and -intolerant chronic myeloid leukemia as well as its full approval for the treatment of therapy-resistant Ph+ acute lymphoblastic leukemia.
Shah
Neil P
NP
Division of Hematology/Oncology, UCSF School of Medicine, San Francisco, California 94143, USA. nshah@medicine.ucsf.edu
D000069439:Dasatinib; D004353:Drug Evaluation, Preclinical; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib