Bosutinib

Bosutinib is a 7-alkoxy-3-quinolinecarbonitrile that functions as a potent, dual SRC and ABL tyrosine kinase inhibitor indicated for chronic myelogenous leukemia (CML), specifically Philadelphia chromosome-positive (Ph+) CML. Philadelphia chromosome is a hallmark of CML due to the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR-ABL fusion protein. The first BCR-ABL inhibitor, imatinib, was introduced over a decade ago as a breakthrough in CML management; however, emerging resistance to imatinib poses challenges in achieving remission. Second-generation BCR-ABL inhibitors like bosutinib inhibit most resistance-conferring BCR-ABL mutations except V299L and T315, thus providing more therapeutic options for patients.

Bosutinib was first approved by the FDA in 2012 for the treatment of adult chronic, accelerated, or blast-phase Ph+ CML with resistance or intolerance to prior therapy. On September 26, 2023, bosutinib was also approved by the FDA for the treatment of pediatric CML that is newly diagnosed or resistant/intolerant to prior therapy. This approval was based on favorable results obtained from the open-label, randomized, multicenter trial BFORE that showed a significant improvement in major molecular response, defined as a ≤0.1% BCR ABL ratio on an international scale, with bosutinib treatment.

用于治疗对既往治疗无效的慢性、加速期或急变期Ph+的慢性粒细胞白血病（CML）患者。