Allosteric enhancement of the BCR-Abl1 kinase inhibition activity of nilotinib by cobinding of asciminib.

ABSTRACT: Inhibitors that bind competitively to the ATP binding pocket in the kinase domain of the oncogenic fusion protein BCR-Abl1 are used successfully in targeted therapy of chronic myeloid leukemia (CML). Such inhibitors provided the first proof of concept that kinase inhibition can succeed in a clinical setting. However, emergence of drug resistance and dose-dependent toxicities limit the effectiveness of these drugs. Therefore, treatment with a combination of drugs without overlapping resistance mechanisms appears to be an appropriate strategy. In the present work, we explore the effectiveness of combination therapies of the recently developed allosteric inhibitor asciminib with the ATP-competitive inhibitors nilotinib and dasatinib in inhibiting the BCR-Abl1 kinase activity in CML cell lines

SUBMITTER: Oruganti B 

PROVIDER: S-EPMC9386466 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature