TGR-1202 and carfilzomib synergistically inhibits translation of c-Myc in lymphoma and myeloma cell lines. The following drugs were used: TG, Ide, Bz, Cfz, IB, TB, IC, TC. (A-B) Levels of c-Myc protein (A) and mRNA (B) in LY10 and LY7 cells treated as indicated for 24 hours. For LY10, TG and Ide were at 3 μM, and Bz and Cfz at 2 nM; for LY7, TG and Ide were at 3 μM, and Bz and Cfz at 5 nM. (C) Schema of a bicistronic luciferase reporter for the translation of c-Myc. IRES, IRES of polio virus; UTR, UTR of c-Myc. (D) Results of the luciferase assay using the bicistronic reporter from panel C. LY7 stably expressing the reporter was treated as indicated for 24 hours. IB-1 and IB-2, Ide 3 μM and 5 μM, respectively, plus Bz 5 nM; TC-1 and TC-2, TG 3 μM and 5 μM, respectively, plus Cfz 5 nM. R:F Luc ratio from the treatment groups was calculated as a percentage of the untreated control, and represents the efficiency of eIF4F cap-dependent translation regulated at the endogenous 5′ UTR of c-Myc. The difference between the TC2 and IB2 treatments was statistically significant; **P of .0013. (E-F) LY7 cells stably transfected with a c-Myc–expressing plasmid (M+) or an EV were treated for 24 hours as indicated. The complementary DNA of c-Myc does not contain the endogenous 5′ UTR. TC-1 and TC-2, TG 3 μM and 5 μM, respectively, plus Cfz 5 nM. Cells were then processed for western blot (E) or Cell Titer Glo to determine viability (F). The difference of viability between the M+ and EV samples was statistically significant; **P < .001. (G-H) The myeloma cell line H929 was stably transduced with an eIF4E-overexpressing plasmid (eIF4E) by lentiviral transduction, or with the corresponding EV. These cells and the untransduced control (No TDX) cells were treated for 24 hours and assessed by western blot (G) and Cell-Titer Glo (H). The difference between the eIF4E and EV samples was statistically significant; **P < .001.