Extended Data Fig. 9: Virtual screening for GGTase I inhibitors.
(a) A workflow of virtual screening for GGTase I inhibitors. (b) The chemical structures and the Docking models of nilotinib, fexinidazole, pilocarpine or zoledronic acid and GGTase I. Imidazolyl was marked with a red circle. (c) MDA-MB-231 cells were treated with 15 μM GGTi-2418 for 16 h, or were treated with 12.5 μM of ketoconazole (KCZ), nilotinib (NOB), fexinidazole (FDZ), pilocarpine (PCP), or zoledronic acid (ZDA) for 48 h prior to Western blot analysis. (d) The replicated experiments of Fig. 8d. MDA-MB-231 or MDA-MB-468 cells were treated with 12.5 μM KCZ or DMSO (-) for 48 h, followed by Western blot analyses. HER2-2+ breast cancer cell line MDA-MB-453 and HER2-1+ breast cancer cell line MDA-MB-175 were used as the positive control. (e) MDA-MB-231 cells stably silencing FBXL2 or MDA-MB-231 cells treated with12.5 μM KCZ for 48 h were subjected to Western blot analyses. (f) MDA-MB-231 or MDA-MB-468 cells were pretreated with or without 12.5 μM KCZ for 48 h, followed by incubation with either 10 μg/mL T-DXd or IgG-DXd for 14-21 days prior to colony formation assays. Scale bar = 1 cm. (g-i) Mice bearing MDA-MB-231 tumors (h, n = 6/group) or MDA-MB-468 tumors (i, n = 5/group) were i.v. administrated with LNP (-) or KCZ@LNP (10 mg/kg, once every day for 2 times) and T-DXd or IgG-DXd (4 mg/kg, one time). The experimental procedure (g) and the body weights of mice (h & i) were shown. Data were presented as mean ± SEM. All blots (c-e) and the images (f) are representative of 3 independent experiments.
