PONATINIB

摘要

Ponatinib (AP-24534) is a third-generation tyrosine kinase inhibitor (TKI) that addresses the clinically concerning BCR-ABL~(T3151)mutation seen in chronic myeloid leukemia (CML). This drug was originally developed as AP-24534, a "pan-BCR-ABL" inhibitor, exhibiting inhibitory effects on all currently known mutations of the BCR-ABL fusion protein. These mutations are estimated to be responsible for 40-50% of treatment failures associated with currently available TKIs. One of the' most common of these mutations is the substitution of the amino acid isoleucine for the threonine at position 315 (T315I). No currently available TKI effectively inhibits this mutation, which results in resistanceand subsequent treatment failure. Early data from preclinical, phase I and phase II clinical studies suggest superior response rates and manageable toxicity, indicating that ponatinib is a promising new agent for the treatment of drug-resistant CML Herein, we will review the available literature regarding ponatinib and its use in CML patients harboring the 7375/ mutation.