Which generation of targeted drugs does Bosutinib belong to? How are the targeting mechanisms different?

Bosutinib is a second-generation BCR-ABLtyrosine kinase inhibitor (TKI ), mainly used to treat patients with chronic myeloid leukemia (CML), especially adult patients who are resistant or intolerant to previous generations of TKI treatments. As a second-generation drug, it has stronger advantages than first-generation drugs in terms of target selectivity and treatment of drug-resistant mutations.

Compared with first-generation TKIcrizotinib (such as imatinib), bosutinib has a higher affinity for BCR-ABLkinase and is Some common resistance mutations (such as Y253H, E255K, etc.) are still active and can still exert efficacy in patients who fail imatinib treatment. Unlike other second-generation TKIs, bosutinib also has inhibitory effects on SRC family kinases, giving it unique advantages in multi-pathway intervention.

The targeting mechanism of Bosutinib is mainly by binding to the BCR-ABL fusion protein kinase domain and blocking its signal transduction process, thereby inhibiting the proliferation of leukemia cells and promoting their apoptosis. Although it is not effective against the T315I mutation (which usually requires a third-generation TKI such as alotinib), bosutinib It performs well in dealing with most non-T315I mutations, making it an important supplementary option in TKI therapy.

In general, bosutinib, as a second-generation TKI, has shown good results in overcoming imatinib resistance and treatment intolerance in patients. It has strong target selectivity and relatively controllable side effects. It is one of the commonly used TKI alternative treatment drugs in the world. For CML patients, bosutinib provides more options for personalized treatment options, especially suitable for some cases that are unresponsive to previous treatments.

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