Solving the Problem of Assessing Synergy and Antagonism for Non-Traditional Dosing Curve Compounds Using the DE/ZI Method: Application to Nrf2 Activators.

Multi-drug combination therapy carries significant promise for pharmacological intervention, primarily better efficacy with less toxicity and fewer side effects. However, the field lacks methodology to assess synergistic or antagonistic interactions for drugs with non-traditional dose response curves. Specifically, our goal was to assess small-molecule modulators of antioxidant response element (ARE)-driven gene expression, which is largely regulated by the Nrf2 transcription factor.