Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants

Christopher A. Eide, Matthew S. Zabriskie, Samantha L. Savage Stevens, Orlando Antelope, Nadeem A. Vellore, Hein Than, Anna Reister Schultz, Phillip Clair, Amber D. Bowler, Anthony D. Pomicter, Dongqing Yan, Anna V. Senina, Wang Qiang, Todd W. Kelley, Philippe Szankasi, Michael C. Heinrich, Jeffrey W. Tyner, Delphine Rea, Jean Michel Cayuela, Dong Wook KimCristina E. Tognon, Thomas O'Hare, Brian J. Druker, Michael W. Deininger

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Most clinical BCR-ABL1 compound mutants are insensitive to current clinical tyrosine kinase inhibitors. Eide et al. show that adding asciminib, an allosteric inhibitor, to ponatinib, an ATP site inhibitor, effectively targets compound mutants and provides a potential mechanism for the collaborative effect.

Original languageEnglish (US)
Pages (from-to)431-443.e5
JournalCancer Cell
Volume36
Issue number4
DOIs
StatePublished - Oct 14 2019

Keywords

  • ABL001
  • allosteric inhibitors
  • asciminib
  • chronic myeloid leukemia
  • compound mutation
  • ponatinib
  • targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Eide, C. A., Zabriskie, M. S., Savage Stevens, S. L., Antelope, O., Vellore, N. A., Than, H., Schultz, A. R., Clair, P., Bowler, A. D., Pomicter, A. D., Yan, D., Senina, A. V., Qiang, W., Kelley, T. W., Szankasi, P., Heinrich, M. C., Tyner, J. W., Rea, D., Cayuela, J. M., ... Deininger, M. W. (2019). Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants. Cancer Cell, 36(4), 431-443.e5. https://doi.org/10.1016/j.ccell.2019.08.004