Fig 2: Binding poses of selected compounds 1a, 1c, 1e, 1g, and 1j (yellow) inside the binding pocket of BCR-ABL. IM (blue), NIL (green). For detailed interaction information, see supplementary materials.

Fig 3: SNIPER(ABL)‐39 inhibits the BCR‐ABL‐related signaling pathway. K562 cells were incubated with the indicated concentration of SNIPER(ABL)‐39 or dasatinib for 6 h. pBCR‐ABL, pSTAT5 and pCrkL stand for phosphorylated BCR‐ABL, STAT5 and CrkL, respectively.

Fig 4: ABL1 phosphorylates MLH1. (A) MLH1 mRNA fold change with ABL1 knockdown (left) or inhibition by imatinib (right) determined by RT-qPCR n = 3 (B) MLH1 immunoprecipitation in HEK293 cells with ABL1 and MLH1 overexpressed followed by immunoblot with anti-phosphotyrosine antibody. Treatment with 5 μM nilotinib reduces the phospho-tyrosine signal associated with MLH1. (C) Kinase assay using recombinant ABL1 (25 ng) and MLH1 (100 ng) protein incubated for 15 min, followed by SDS-PAGE and immunoblot analysis indicates tyrosine phosphorylation of MLH1 only in the presence of ABL1 kinase.

Fig 5: MLH1 binds to Hsp70 in the absence of ABL1 signaling and inhibition of Hsp70 restores MLH1 levels. (A) MLH1 immunoprecipitation from nuclear or cytoplasmic fractions in cells transfected with scrambled control or ABL1 siRNA followed by immunoblot for Hsp70 and MLH1. Cytoplasmic and nuclear fractionation purity was confirmed by GAPDH and Histone H3 immunoblots, respectively. Quantification of percent MLH1 bound to Hsp70 is shown. n = 3, significance was determined by unpaired t-test *p < 0.05. (B) MLH1 immunoprecipitation from whole cell lysate of HEK293 cells overexpressing MLH1 and treated with nilotinib or vehicle control, followed by immunoblot for Hsp70 and MLH1 (C) Immunoblot analysis and quantification of MLH1 protein expression in HEK293 cells after treatment with nilotinib or vehicle control after 24 h of co-treatment with 1 μM Hsp70 inhibitor, YM-01, or vehicle control. n = 3, significance was determined by unpaired t-test *p < 0.05.