Figure 3.
Two synergistic combination models to optimize hits from drug repositioning screens. (a) Synergistic combination to reduce toxicity when drug 1, drug 2 or drug 3 showed 90% efficacy at single use, the drug concentration will trigger severe toxicity (e.g., 60%). Through synergistic combination, the combined efficacy is not reduced but each drug concentration was reduced to 1/10, leading to a lower toxicity (e.g., 6%). (b) Synergistic combination to match in vivo dosage. When drug 1, drug 2 or drug 3 showed 90% efficacy at single use, the drug concentration is fivefold of their allowed in vivo dosages (Cmean or Cmax). Through synergistic combination, the combined efficacy is not reduced but each drug concentration was reduced to 1/10, reaching the allowed in vivo concentration (1/2 of Cmean or Cmax).