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Dasatinib, at nanomolar concentrations can inhibit the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, it is predicted to bind to multiple conformations of the ABL kinase. In vitro, it is active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib can inhibit the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Dasatinib is able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.
• Adult Patients with newly diagnosed Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
• Adult Patients with Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib.
• Adult Patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) who no longer benefit from, or did not tolerate, other treatment.
•Children 1 year of age and older with Ph+ CML in chronic phase; and children 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy.