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. 2021 Oct 29;12:741219. doi: 10.3389/fphar.2021.741219

FIGURE 4.

FIGURE 4

Target identification and validation of SC75741. (A). Molecular docking models of SC75741 with c-Abl (PDB code: 1IEP). The imatinib is shown in red and SC75741 is shown in green. The hydrogen-bonding interactions are shown using red lines. Detailed interactions of SC75741 with c-Abl was amplified as shown in the right. (B). Dose–response curves of c-Abl activity in the presence of SC75741. (data represent from at least two independent experiments). (C). H4GT25 cells were pretreated with 1 μg/ml DOX for 24 h, treated with DMSO, CAPE (10 μM), JSH-23 (10 μM), PP-121 (5 μM), imatinib (5 μM) or SC75741 (5 μM) for another 24 h. Cell lysates were immunoblotted with indicated antibodies. The numbers under the blot represent the gray scale quantification (GFP/Tubulin, p-c-Abl(T245)/Tubulin, c-Abl/Tubulin). (D). H4GT25 cells were pretreated with 1 μg/ml DOX for 24 h, treated with 1 μM MG132 for 12 h, treated with DMSO, PP-121 (5 μM), imatinib (5 μM) or SC75741 (5 μM) for another 24 h. Cell lysates were immunoblotted with indicated antibodies. The numbers under the blot represent the gray scale quantification (GFP/Tubulin). (E). H4GT25 cells were pretreated with 1 μg/mL DOX for 24 h, treated with 0.5 mM arsenite for 1 h, treated with DMSO, PP121 (5 μM), imatinib (5 μM) or SC75741 (5 μM) for another 24 h. Cell lysates were immunoblotted with indicated antibodies. The numbers under the blot represent the gray scale quantification (GFP/Tubulin). (F). SH-SY5Y cells were transfected with indicated plasmids for 24 h, treated with DMSO, PP121 (5 μM), imatinib (5 μM) or SC75741 (5 μM) for another 24 h, Cell lysates were immunoblotted with indicated antibodies. The numbers under the blot represent the gray scale quantification (GFP/Tubulin). (G). H4GT25 cells were pretreated with 1 μg/ml DOX for 24 h, treated with DMSO, PP-121 (5 μM), imatinib (5 μM) or SC75741 (5 μM) for another 24 h, total lysates, RIPA lysates and urea lysates were immunoblotted with indicated antibodies. The numbers under the blot represent the gray scale quantification (GFP/Tubulin).