The new allosteric inhibitor asciminib is susceptible to resistance mediated by ABCB1 and ABCG2 overexpression in vitro.

ABSTRACT: Asciminib (previously ABL001), which binds the myristate-binding pocket of the Bcr-Abl kinase domain, is in phase I clinical trials as monotherapy and in combination with imatinib, nilotinib and dasatinib for the treatment of patients with refractory CML or Ph+ ALL. Asciminib sensitivity was evaluated in asciminib naïve BCR-ABL1+ cell lines K562 (negligible ABCB1/ABCG2 expression), K562-Dox (ABCB1-overexpressing through doxorubicin exposure) and K562-ABCG2 (ABCG2 overexpression via transduction) with results demonstrating asciminib efflux by both ABCB1 and ABCG2 transporters. K562-Dox and K562-ABCG2 cells demonstrated increased LD50^asciminib vs K562 control cells: 256 and 299 nM respectively vs 24 nM, p < 0.001. Sensitivity was completely restored with specific inh

SUBMITTER: Eadie LN 

PROVIDER: S-EPMC5862588 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature