Discovering Anti-platelet Drug Combinations with an Integrated Model of Activator-Inhibitor Relationships, Activator-Activator Synergies and Inhibitor-Inhibitor Synergies
Fig 6
Synergy is defined as occurring where the double dose of either of the two individual reagents result in significantly less inhibition than the combination of single doses together. Reagents are labelled as with the suffix “i” indicating inhibitor. Label without a number indicates the chosen (typically 50% activation) dose for the inhibitor. The prefix “2” indicates a doubling of this dose. The prefix “90” indicates the dose chosen to approximate 90% activation by the reagent. “Log response" on the horizontal axis refers to the log10 luminescence of the measured arbitrary absorbance units (AAU). The cocktail of activators is included in each experiment with the indicated inhibitors (excluding the “Resting” control of unactivated platelets). Small *: significant difference from the double dose of the indicated inhibitor, by one-tailed Wilcoxon test P < 0.05. Large *represents where both tests are significant(c, e and f). Combinations are shown for the following inhibitor pairs (A) Ai and Ti (B) Ai and Pi (C) Ti and Pi (D) Xi and Ai (E) Xi and Ti (F) Xi and Pi (G) Xi and Ei (H) Ei and Ai (I) Ei and Ti (L) Ei and Pi.