Fig. 4

PTC-209 reduces the effect of major myeloma growth factors and stromal support as well as displays synergistic activity with pomalidomide and carfilzomib. a PTC-209 was found to impair the growth and survival-propagating effects of IGF-1 and IL-6 in a dose-dependent manner. b The anti-MM activity of PTC-209 was upheld in the presence of BM stromal cells and promoted the activity of pomalidomide and carfilzomib. ***P < 0.001, **P < 0.01 and *P < 0.05 vs PBS control; ^### P < 0.001, ^## P < 0.01 and ^# P < 0.05 vs IGF-1 control; ⁺⁺⁺ P < 0.001, ⁺⁺ P < 0.01 and ⁺ P < 0.05 vs IL-6 control. c Additive/synergistic activity of drug combinations was confirmed by concurrent treatment of MM cell lines with PTC-209 and either pomalidomide or carfilzomib for 96 h at varying concentrations. Graphs for MM.1S and U266 are representative for the panel of HMCLs analysed. Combination index (CI) values were determined with CompuSyn. CI values <0.8, 0.8–1.2, or >1.2 indicate synergistic, additive or antagonistic drug activities, respectively