Synergistic drug effects on growth of HMC-1 cells. HMC-1.1 cells lacking KIT D816V (A-F) and HMC-1.2 cells exhibiting KIT D816V (G-J) were incubated with control medium or various combinations of drugs (at a fixed ratio) as indicated, at 37°C for 48 hours to determine cooperative antiproliferative effects. (A,C,E,G,I) After incubation with single drugs (A) PKC412 (▪) and AMN107 (•); (C) imatinib (▪) and AMN107 (•); (E) imatinib (▪) and PKC412 (•); (G) PKC412 (▪) and AMN107 (•); (I) PKC412 (▪) and 2CdA (•) or drug combinations (▴), cells were analyzed for ³H-thymidine uptake. Results show ³H-thymidine uptake as percentage of control (medium control, 100%) and represent the mean ± SD of triplicates from one typical experiment (corresponding results were obtained in at least 2 other experiments for each drug combination). Images in the bottom row (B,D,F,H,J) show combination index values determined for each fraction affected according to the method described by Chou and Talalay³⁹  using Calcusyn software. A combination index (CI) value of 1.0 indicates an additive effect, a CI greater than 1.0 indicates antagonism, and a CI of less than 1.0 indicates synergism.