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<p>The distribution of tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) is influenced by the efflux transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). While most TKI-transporter interactions are well established, limited information is available for the novel STAMP inhibitor asciminib, and divergent data exist for the role of P-gp in nilotinib and bosutinib efflux. This study used in vitro cellular and vesicular transport assays to evaluate the substrate and inhibitory profiles of all TKIs currently used in CML treatment. It was confirmed that asciminib is a substrate of both P-gp and BCRP, similar to imatinib and dasatinib, whereas bosutinib was modestly transported by P-gp only. For P-gp, asciminib appeared to be a weak inhibitor, comparable to dasatinib, whereas nilotinib remained the most potent inhibitor. Conversely, asciminib demonstrated notable potency against BCRP, ranking it among the strong inhibitors imatinib, nilotinib, and ponatinib, while dasatinib and bosutinib were less effective. These findings provide further insight into the efflux transporter interactions of asciminib and updated evidence on nilotinib and bosutinib transport by P-gp, with implications for drug resistance and treatment optimization in CML.</p>

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Characterizing P-glycoprotein and Breast Cancer Resistance Protein interactions of asciminib among other tyrosine kinase inhibitors used in chronic myeloid leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月12日

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  • N. E. Verhagen,
  • D. C.W. Touw,
  • J. J.M.W. van den Heuvel,
  • P. H. van den Broek,
  • N. M.A. Blijlevens,
  • J. J.W.M. Janssen,
  • J. B. Koenderink,
  • F. G.M. Russel

摘要

The distribution of tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) is influenced by the efflux transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). While most TKI-transporter interactions are well established, limited information is available for the novel STAMP inhibitor asciminib, and divergent data exist for the role of P-gp in nilotinib and bosutinib efflux. This study used in vitro cellular and vesicular transport assays to evaluate the substrate and inhibitory profiles of all TKIs currently used in CML treatment. It was confirmed that asciminib is a substrate of both P-gp and BCRP, similar to imatinib and dasatinib, whereas bosutinib was modestly transported by P-gp only. For P-gp, asciminib appeared to be a weak inhibitor, comparable to dasatinib, whereas nilotinib remained the most potent inhibitor. Conversely, asciminib demonstrated notable potency against BCRP, ranking it among the strong inhibitors imatinib, nilotinib, and ponatinib, while dasatinib and bosutinib were less effective. These findings provide further insight into the efflux transporter interactions of asciminib and updated evidence on nilotinib and bosutinib transport by P-gp, with implications for drug resistance and treatment optimization in CML.