Receptor

Ponatinib

Bioinformatics

Biology

Gene

Mutant

Allosteric regulation

Chemistry

Imatinib

Myeloid leukemia

Dasatinib

Drug discovery

Cell biology

Cancer research

Genetics

Pharmacology

Cancer Cell

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.

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