ArticleFrontiers in pharmacology2021
Solving the Problem of Assessing Synergy and Antagonism for Non-Traditional Dosing Curve Compounds Using the DE/ZI Method: Application to Nrf2 Activators.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- The oxidative stress paradigm in arbovirus infections: mechanisms and therapeutic insights.Redox report : communications in free radical research · 2026Review
- Sulforaphane improves exercise-induced NRF2 signaling in older adults: an in vivo-ex vivo approach.GeroScience · 2026Article
- Targeting Oral Pathogens withAntibiotics (Basel, Switzerland) · 2025Article
- Identification of YAP regulators through high-throughput screening and NanoBiT-based validation-drug repositioning for cancer therapy.Animal cells and systems · 2025Article
- Exploring the Therapeutical Potential ofMarine drugs · 2024Article
- Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2.International journal of molecular sciences · 2024Review
- Acute Oxidative Stress Can Paradoxically Suppress Human NRF2 Protein Synthesis by Inhibiting Global Protein Translation.Antioxidants (Basel, Switzerland) · 2023Article
- The Use of Acute Immunosuppressive Therapy to Improve Antibiotic Efficacy against Intracellular Staphylococcus aureus.Microbiology spectrum · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. Known as Nrf2 activators, this class of compounds upregulates a battery of cytoprotective genes and shows significant promise for prevention of numerous chronic diseases. For example, sulforaphane sourced from broccoli sprouts is the subject of over 70 clinical trials. Nrf2 activators generally have non-traditional dose response curves that are hormetic, or U-shaped. We introduce a method based on the principles of Loewe Additivity to assess synergism and antagonism for two compounds in combination. This method, termed Dose-Equivalence/Zero Interaction (DE/ZI), can be used with traditional Hill-slope response curves, and it also can assess interactions for compounds with non-traditional curves, using a nearest-neighbor approach. Using a Monte-Carlo method, DE/ZI generates a measure of synergy or antagonism for each dosing pair with an associated error and
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