Fig. 2. Mebendazole (MBZ) suppresses BCR/ABL kinase activity and downstream signaling pathways by binding the ATP-binding site of BCR/ABL kinase.
(A, B) Western blot was used to measure protein expression of BCR/ABL, p-BCR/ABL, STAT5, p-STAT5 and signaling molecules in the RAS/RAF/MEK/ERK signaling pathway after MBZ treatment for 24 h. (C) In vitro validation of protein kinase inhibition by MBZ. Staurosporine was used as a positive control to inhibit the kinase activity of ABL1. The values are the mean ± SD of three independent experiments. (D) The molecular structure of MBZ. (E) The molecular structure of imatinib. (F) The binding pose and interactions of imatinib (magenta) with co-crystallized BCR/ABL kinase in the crystal structure (PDB ID: 1IEP) and predicted docking orientation of imatinib (yellow) in silico docking analysis. (G) The predicted binding pose of MBZ (red) in BCR/ABL tyrosine kinase (green, PDB ID: 1IEP) with a binding affinity of −9.0 kcal/mol. Key amino acid residues are visualized in sticks. Hydrogen bonds (green), hydrophobic interactions (pink), π-stacking (cyan) and salt bridges (yellow) are indicated as dashed lines.
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