Exploring the Allosteric Pathways of Asciminib in the Dual Inhibition of BCR-ABL1.

ABSTRACT: The BCR-ABL1 fusion protein is a critical therapeutic target in Chronic Myeloid Leukemia (CML). Current monotherapy approaches involve types of inhibitors that can be categorized into ATP competitive inhibitors and allosteric inhibitors. However, resistance mutations in the tyrosine kinase domain of BCR-ABL1 have limited the effectiveness of these drugs. Research indicates that dual inhibition of BCR-ABL1 by combining these two types of inhibitors effectively addresses the issue of drug resistance as there are no overlapping resistance mechanisms. However, the underlying reasons for the observed synergistic effects have not yet been thoroughly elucidated. In this study, we employed molecular dynamics simulation to observe the synergistic interactions of BCR-ABL1 by the allosteric inhibitor

SUBMITTER: Ming J 

PROVIDER: S-EPMC12467782 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature