Is Bosutinib a second- or third-generation drug?

Bosutinib is an oral tyrosine kinase inhibitor (TKI) mainly used for the treatment of chronic myelogenous leukemia (CML). In the development process of TKI drugs, bosutinib is classified as a second-generation tyrosine kinase inhibitor. The first-generation TKI, represented by Imatinib, mainly acts on the BCR-ABL fusion protein and is a pioneering drug in the treatment of chronic myelogenous leukemia. With the improvement of clinical needs, some patients have developed resistance or intolerance to first-generation TKIs. Some second-generation drugs such as dasatinib, nilotinib and bosutinib have emerged to solve the problem of resistance or adverse reactions.

Compared with first-generation drugs, bosutinib has higher target selectivity and the ability to inhibit resistance to certain BCR-ABL mutations, but it is not a third-generation TKI. Third-generation TKIs such as ponatinib are mainly used for CML patients who are resistant to second-generation drugs or have T315I mutation. Bosutinib is designed to optimize tolerability while providing an effective alternative in second-line therapy. In clinical practice, bosutinib is usually used for patients with chronic phase CML who are resistant or intolerant to imatinib. It can also be used as an initial treatment option in certain circumstances, but its main advantages are still its second-line efficacy and good safety.

Bosutinib blocks abnormal leukocyte proliferation by inhibiting theBCR-ABL signaling pathway. It also has a certain inhibitory effect on Src family kinases, thereby exerting a therapeutic effect in advanced or drug-resistant patients. Its oral administration method allows patients to maintain treatment for a long time in a home environment, while monitoring blood, liver function and cardiovascular indicators during the course of treatment to ensure a balance between drug safety and efficacy. Second-generation TKIs are characterized by controllable side effects and stable efficacy, and are suitable for use by CML patients who require long-term maintenance treatment.

Reference materials:https://go.drugbank.com/drugs/DB06616