Figure 2From: Systems biology approaches for advancing the discovery of effective drug combinations Examples of Loewe Additivity and Bliss Independence in defining drug interactions. A) Additivity, synergy and antagonism of drug combination as defined by Loewe Additivity. Let x and y-axes represent concentrations of drugs A and B to achieve a defined effect X% (e.g., X = 50% for half maximal inhibitory concentration (IC50) of [I A]50% and [I B]50%), respectively. The coordinates ([I A]50%,0) and (0, [I B]50%) represent the concentration for drugs A and B, respectively. The line of additivity is constructed by connecting these two points for a 50% effect isobologram plot. The concentrations of the two drugs used in combination to provide the same effect X% (e.g. X = 50%) will be denoted by point ([C A]50%,[C B]50%) and are placed in the same plot. Synergy, additivity, or antagonism will be determined when this point ([C A]50%,[C B]50%) is located below, on, or above the line, respectively. More generally, linear, concave, and convex isoboles represent non-interacting, synergy, and antagonistic drug combination, respectively. B) Additivity, synergy and antagonism of drug combination as defined by Bliss Independence. For example, if two non-interacting drugs (A and B) each result in 40% tumor growth compared to control (E A = 0.4, E B = 0.4), then the predicted tumor growth when combined would be E C = (0.4 x 0.4) = 0.16, (16% of control). If the observed combined (A + B, red bar) tumor growth is similar to, less than, or greater than 16% of control, then the combination would be deemed as additive, synergistic, or antagonistic, respectively. N.D. denotes no drug (control).Back to article page