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Figure 2 | Journal of Cheminformatics

Figure 2

From: Systems biology approaches for advancing the discovery of effective drug combinations

Figure 2

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).

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