Fig. 5.

Drug synergism between mitotane and proteasome inhibitors. Normalized isobolograms (a and c) and corresponding dose-reduction index (DRI) tables (b and d) for combination treatment with bortezomib and mitotane (a and b) and carfilzomib and mitotane (c and d). The diagonal line represents a cooperativity index of 1 indicating additive drug interaction of the combined treatment. Drug combinations below the curve indicate synergism, the area over the curve antagonism. Fa, fraction affected; BTZ, bortezomib; CFZ, carfilzomib; MITO, mitotane; DRI, dose-reduction index for the combination treatment; [nM], concentration range in nanomoles/litre and [μM], concentration range in micromoles/litre where the synergistic effect is observed