MECHANISM OF ACTION

» Dasatinib inhibits multiple tyrosine kinases including BCR-ABL, the fusion protein created by the abnormal Philadelphia chromosome (Ph) which characterizes chronic myeloid leukemia.

» Competitive inhibition at the enzyme’s ATP-binding site leads to inhibition of tyrosine phosphorylation of proteins involved in BCR-ABL signal transduction.

» Inhibition is not completely selective, as dasatinib also inhibits other kinases including the Src family (LYN, HCK), c-kit, ephrin receptor (EPH), and platelet-derived growth factor receptor (PDGFβ). 2

Dasatinib is structurally unrelated to imatinib and is approximately 300-fold more potent in terms of BCR-ABL inhibition.