We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Anticancer potential of mebendazole against chronic myeloid leukemia: in silico and in vitro studies revealed new insights about the mechanism of action.
- Authors
Paulino Daniel, Julio; Pantoja Mesquita, Felipe; Lucena Da Silva, Emerson; Noronha de Souza, Pedro Filho; Benevides Lima, Luina; Brasil de Oliveira, Lais Lacerda; Amaral de Moraes, Maria Elisabete; Aquino Moreira-Nunes, Caroline de Fátima; Rodríguez Burbano, Rommel Mario; Zanatta, Geancarlo; Carvalho Montenegro, Raquel
- Abstract
Chronic myeloid leukemia (CML) is caused by constitutively active fusion protein BCR-ABL1, and targeting ABL1 is a promising therapy option. Imatinib, dasatinib, and nilotinib have all been shown to work effectively in clinical trials. ABL1 mutations, particularly the T315I gate-keeper mutation, cause resistance in patients. As a result, broad-spectrum ABL1 medicines are desperately needed. In order to screen potential drugs targeting CML, mebendazole (MBZ) was subjected to the in vitro test against CML cell lines (K562 and FEPS) and computational assays. The antiproliferative effect of MBZ and the combination with tyrosine kinase inhibitors (TKIs) was tested using end-point viability assays, cell cycle distribution analysis, cellmembrane, andmitochondrial dyes. By interrupting the cell cycle and causing cell death, MBZ and its combination with imatinib and dasatinib have a significant antiproliferative effect. We identified MBZ as a promising "new use" drug targeting wild-type and mutant ABL1 using molecular docking. Meanwhile, we determined which residues in the allosteric site are important in ABL1 drug development. These findings may not only serve as a model for repositioning current authorized medications but may also provide ABL1-targeted anti-CML treatments a fresh lease of life.
- Subjects
CHRONIC myeloid leukemia; PROTEIN-tyrosine kinase inhibitors; IN vitro studies; CELL cycle; TARGETED drug delivery
- Publication
Frontiers in Pharmacology, 2022, Vol 13, p1
- ISSN
1663-9812
- Publication type
Article
- DOI
10.3389/fphar.2022.952250