The Sound of Evolution
Imatinib
Mechanism of action:
Imatinib is a tyrosine kinase inhibitor. In chronic myelogenous leukemia, the 9;22 chromosomal translocation produces the BCR-ABL fusion gene, also known as the Philadelphia chromosome. This fusion protein has constitutively active tyrosine kinase activity, escapes normal regulation, and drives uncontrolled proliferation of leukemic cells. Imatinib binds to the ATP-binding site of the ABL kinase, locking it into an inactive conformation and preventing phosphorylation and downstream signal transduction. This blocks the activation of downstream pathways such as RAS-MAPK, PI3K-AKT, and JAK-STAT, leading tumor cells to stop proliferating and undergo apoptosis.
Reference(s):
1. Deininger MW et al. (2003). Specific targeted therapy of chronic myelogenous leukemia with imatinib. Pharmacol Rev.
2. Vigneri P et al. (2001). Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase. Nat Med.
3. Droogendijk HJ et al. (2006). Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer.