S63845 and venetoclax synergize in vivo and activate apoptosis. (A) DLBCL cell line SU-DHL-6 was xenografted subcutaneously into NSG female mice. After 10 days, mice were randomly assigned into comparable groups (5 mice each) and treated with vehicle (Veh), venetoclax (Ven) (100 mg/kg orally 5 times per week), S63845 (25 mg/kg IV 5 times per week), and a combination of venetoclax (100 mg/kg orally 5 times per week) and S63845 (25 mg/kg IV 5 times per week) for 2 weeks (indicated by black line). Tumor volumes are represented as means; error bars represent SD. (B) Kaplan-Meier survival curve (survival percentage) of tumor-bearing mice treated as specified in panel A. (C) Immunohistochemistry (IHC) images at original magnification ×40 of mouse tumors from SU-DHL-6 xenografts exposed to different treatment groups described in panel A stained for cleaved caspase-3. (D) Quantification of cleaved caspase-3–positive cells in IHC images of mouse tumors in panel C. (E) Western blot analysis of protein derived from tumors to assess the effects of different drug treatments indicated in panel A. In vivo protein levels of poly (ADP-ribose) polymerase (PARP) and cleaved PARP were assessed on day 5 of treatment. β-Actin was used as a loading control.