What genes does bosutinib/bosutinib target?

Bosutinib/Bosutinib is an important tyrosine kinase inhibitor mainly used to treat Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Its mechanism of action involves the inhibition of multiple target genes, especially the potent inhibition of BCR-ABL kinase. BCR-ABL kinase is a tyrosine kinase formed by the fusion of BCR and ABL genes and is a key factor in promoting the proliferation and survival of CML cells. Bosutinib binds to BCR-ABL and blocks the signal transduction pathway, thereby effectively inhibiting the growth of tumor cells.

In addition to inhibitingBCR-ABL, bosutinib also has a significant inhibitory effect on Src family kinases, including Src, Lyn and Hck. These kinases play important roles in a variety of cell signaling processes and are closely related to cell proliferation, migration, and survival. By inhibiting the activity of these kinases, bosutinib further enhances its anti-tumor effect and helps control the progression of CML patients.

In addition, bosutinib has shown good efficacy in imatinib-resistantCML cells. Studies have shown that bosutinib inhibits 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines. This property makes bosutinib a strong option for patients who have developed resistance to conventional treatments and is critical to improving their treatment outcomes. However, bosutinib did not show significant inhibitory effects on certain mutant types of BCR-ABL kinase, such as T315I and V299L mutant cells. The T315I mutation is one of the common drug-resistant mutations in CML patients, so the use of bosutinib may be limited for patients with this type of mutation.

In general, bosutinib exerts its effect in inhibiting tumor growth by targetingBCR-ABL kinase and Src family kinases. Its unique advantages in the treatment of CML make it not only suitable for treatment-naïve patients, but also provides a new treatment option for patients facing drug resistance challenges.

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