Dasatinib

The BCR-ABL oncogene triggers intracellular signaling, activating multiple transduction cascades, promoting the growth, proliferation and survival of hematopoietic cells. BCR-ABL plays a role in defective DNA repair, alteration of cellular adhesion and inhibition of apoptosis. Degregulated BCR-ABL tyrosine kinase activity is the molecular marker for CML. Inhibiting BCR-ABL tyrosine kinase activity leads to the induction of apoptosis and inhibits cellular proliferation in vitro and there are various BCR-ABL isoforms with differing activity levels as well. Dasatinib (BMS-354825, Sprycel®) is a potent multi-target kinase inhibitor of BCR-ABL. Dasatiinib performs better against ABL kinase than earlier drugs such as imatinib, and Dasatinib also is effective against SRC family of kinases, and other receptor kinases such as EPHA2, PDGFR, and c-Kit. Dasatinib's inhibiting potential against Src family kinase members is greater (IC(50) 0.5nM) than its inhibitory activity against ABL (1nM).