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Axitinib Effectively Inhibits BCR-ABL1(T315I) with a Distinct Binding Confirmation

Pemovska T., Johnson E., Kontro M., Repasky G., Chen J., Wells P, Ciaran N., Cronin C., McTigue M.,

Institute for Molecular Medicine Finland; University of Helsinki; La Jolla Laboratories, Pfizer

ABSTRACT:

The BCR-ABL1 fusion gene is a driver oncogene in chronic myeloid leukaemia and 30–50% of cases of adult acute lymphoblastic leukaemia1. Introduction of ABL1 kinase inhibitors (for example, imatinib) has markedly improved patient survival2, but acquired drug resistance remains a challenge3, 4, 5. Point mutations in the ABL1 kinase domain weaken inhibitor binding6 and represent the most common clinical resistance mechanism...

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