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

1 Citation (Scopus)

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

Fingerprint

Protein-Tyrosine Kinases
Adenosine Triphosphate
ponatinib

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Eide, C. A., Zabriskie, M. S., Savage Stevens, S. L., Antelope, O., Vellore, N. A., Than, H., ... 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

Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants. / Eide, Christopher A.; Zabriskie, Matthew S.; Savage Stevens, Samantha L.; Antelope, Orlando; Vellore, Nadeem A.; Than, Hein; Schultz, Anna Reister; Clair, Phillip; Bowler, Amber D.; Pomicter, Anthony D.; Yan, Dongqing; Senina, Anna V.; Qiang, Wang; Kelley, Todd W.; Szankasi, Philippe; Heinrich, Michael C.; Tyner, Jeffrey W.; Rea, Delphine; Cayuela, Jean Michel; Kim, Dong Wook; Tognon, Cristina E.; O'Hare, Thomas; Druker, Brian J.; Deininger, Michael W.

In: Cancer Cell, Vol. 36, No. 4, 14.10.2019, p. 431-443.e5.

Research output: Contribution to journalArticle

Eide, CA, Zabriskie, MS, Savage Stevens, SL, Antelope, O, Vellore, NA, Than, H, Schultz, AR, Clair, P, Bowler, AD, Pomicter, AD, Yan, D, Senina, AV, Qiang, W, Kelley, TW, Szankasi, P, Heinrich, MC, Tyner, JW, Rea, D, Cayuela, JM, Kim, DW, Tognon, CE, O'Hare, T, Druker, BJ & Deininger, MW 2019, 'Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants', Cancer Cell, vol. 36, no. 4, pp. 431-443.e5. https://doi.org/10.1016/j.ccell.2019.08.004
Eide, Christopher A. ; Zabriskie, Matthew S. ; Savage Stevens, Samantha L. ; Antelope, Orlando ; Vellore, Nadeem A. ; Than, Hein ; Schultz, Anna Reister ; Clair, Phillip ; Bowler, Amber D. ; Pomicter, Anthony D. ; Yan, Dongqing ; Senina, Anna V. ; Qiang, Wang ; Kelley, Todd W. ; Szankasi, Philippe ; Heinrich, Michael C. ; Tyner, Jeffrey W. ; Rea, Delphine ; Cayuela, Jean Michel ; Kim, Dong Wook ; Tognon, Cristina E. ; O'Hare, Thomas ; Druker, Brian J. ; Deininger, Michael W. / Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants. In: Cancer Cell. 2019 ; Vol. 36, No. 4. pp. 431-443.e5.
@article{c3335de2981e436486169523bf004c3f,
title = "Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants",
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.",
keywords = "ABL001, allosteric inhibitors, asciminib, chronic myeloid leukemia, compound mutation, ponatinib, targeted therapy",
author = "Eide, {Christopher A.} and Zabriskie, {Matthew S.} and {Savage Stevens}, {Samantha L.} and Orlando Antelope and Vellore, {Nadeem A.} and Hein Than and Schultz, {Anna Reister} and Phillip Clair and Bowler, {Amber D.} and Pomicter, {Anthony D.} and Dongqing Yan and Senina, {Anna V.} and Wang Qiang and Kelley, {Todd W.} and Philippe Szankasi and Heinrich, {Michael C.} and Tyner, {Jeffrey W.} and Delphine Rea and Cayuela, {Jean Michel} and Kim, {Dong Wook} and Tognon, {Cristina E.} and Thomas O'Hare and Druker, {Brian J.} and Deininger, {Michael W.}",
year = "2019",
month = "10",
day = "14",
doi = "10.1016/j.ccell.2019.08.004",
language = "English (US)",
volume = "36",
pages = "431--443.e5",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants

AU - Eide, Christopher A.

AU - Zabriskie, Matthew S.

AU - Savage Stevens, Samantha L.

AU - Antelope, Orlando

AU - Vellore, Nadeem A.

AU - Than, Hein

AU - Schultz, Anna Reister

AU - Clair, Phillip

AU - Bowler, Amber D.

AU - Pomicter, Anthony D.

AU - Yan, Dongqing

AU - Senina, Anna V.

AU - Qiang, Wang

AU - Kelley, Todd W.

AU - Szankasi, Philippe

AU - Heinrich, Michael C.

AU - Tyner, Jeffrey W.

AU - Rea, Delphine

AU - Cayuela, Jean Michel

AU - Kim, Dong Wook

AU - Tognon, Cristina E.

AU - O'Hare, Thomas

AU - Druker, Brian J.

AU - Deininger, Michael W.

PY - 2019/10/14

Y1 - 2019/10/14

N2 - 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.

AB - 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.

KW - ABL001

KW - allosteric inhibitors

KW - asciminib

KW - chronic myeloid leukemia

KW - compound mutation

KW - ponatinib

KW - targeted therapy

UR - http://www.scopus.com/inward/record.url?scp=85072922152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072922152&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2019.08.004

DO - 10.1016/j.ccell.2019.08.004

M3 - Article

C2 - 31543464

AN - SCOPUS:85072922152

VL - 36

SP - 431-443.e5

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 4

ER -