The Sound of Evolution
Dasatinib
Mechanism of action:
Dasatinib is a second-generation tyrosine kinase inhibitor. Dasatinib primarily targets the BCR-ABL fusion protein, which is produced by the fusion gene on the Philadelphia chromosome (t(9;22)(q34;q11)) formed through chromosomal translocation in chronic myeloid leukemia (CML). BCR-ABL is a constitutively active tyrosine kinase that excessively stimulates cell growth and suppresses apoptosis, leading to leukemia. Dasatinib binds to the ATP-binding site of BCR-ABL, blocking activation of downstream signaling molecules such as STAT5, PI3K, and MAPK. This deprives cancer cells of proliferative signaling and induces apoptosis.
Reference(s):
1. Das J et al. (2006). 2-aminothiazole as a novel kinase inhibitor template: Structure-activity relationship studies toward the discovery of dasatinib (BMS-354825) as a potent pan-Src kinase inhibitor. J Med Chem.
2. Talpaz M et al. (2006). Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med.