The conjugates with the PEG-linker exhibited improved inhibition on colony formation and antitumor efficacy in vivo. (A) Bcl-2 inhibition and cell growth inhibition in U937 cells following treatment with A18 to A20 with an extended PEG-linker. (B) Apoptosis induction in U937 cells treated with 0.8 μM of each compound for 24 hours. (C) The relative protein levels of U937 cells treated with each compound for 24 hours. (D) Colony forming inhibition of U937 cells treated with each compound for 14 days. (E) The scheme of treatment of U937 xenografts cells. (F) Tumors of U937 xenografts dissected at the end of experiment. (G) Tumor weights and mean values of U937 xenografts (n = 5). ∗∗∗P < .001 when compared with the control group. ###P < .001, 2-group analysis. (H) Tumor growth rates of U937 xenografts during the treatment. (I) Body weights of mice that received U937 xenografts during the treatment. (J) Tumors that developed from MOLM-13/VEN xenografts after dissection at the end of the experiment. (K) Tumor weights and mean values of MOLM-13/VEN xenografts cells (n = 5). ∗∗∗P < .001 when compared with the control group. ##P < .01; ###P < .001, 2-group analysis. (L) Tumor growth rates of MOLM-13/VEN xenografts during the treatment. (M) Body weights of mice that received MOLM-13/VEN xenografts during the treatment. Con, control; IC50, 50% inhibitory concentration; PO, by mouth; IP, intraperitoneally.
