Ponatinib

Ponatinib is a tyrosine kinase inhibitor. In chronic myelogenous leukemia, a 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. Ponatinib binds to the ATP-binding site of ABL kinase and locks it into an inactive conformation, thereby blocking phosphorylation and downstream signal transduction. As a result, pathways such as RAS-MAPK, PI3K-AKT, and JAK-STAT cannot be activated, leading tumor cells to stop proliferating and undergo apoptosis.