ArticleNature biotechnology2009
Synergistic drug combinations tend to improve therapeutically relevant selectivity.
Article in Nature biotechnology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 419 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
419 citing papers in PubMed, 946 citations in OpenAlex.
- FDA-approved IMPDH inhibitors synergize with ribavirin to inhibit respiratory syncytial virus by interfering with purineEmerging microbes & infections · 2026Article
- Anti-psychotic drugs act synergistically in combination with antifungal drugs to inhibit drug-resistantmSphere · 2026Article
- The Combination of Nirmatrelvir and Ivermectin Exerts Strongly Synergistic Antiviral and Anti-Inflammatory Effects Against Murine Coronavirus Infection of Macrophages.International journal of molecular sciences · 2026Article
- Epigenetic Control of Stress-Induced Depression: Emerging Roles of HDAC3 and HDAC6.International journal of molecular sciences · 2026Review
- Structural Modifications of Hybrid O-Alkylsulfonyl-β-(Benzimidazol-1-yl)propioamidoximes as a Pathway to the Antimicrobial, Antifungal and Antidiabetic Drugs.International journal of molecular sciences · 2026Article
- A dual granular balanced deep forest model for effective drug combination prediction.iScience · 2026Article
- Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition.Molecular therapy. Oncology · 2026Article
- Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases.iScience · 2026Article
- In Vitro/In Silico Potential of High-Yield Essential Oils for Management of Postharvest Fungi.Metabolites · 2026Article
- A comprehensive review of cluster methods for drug-drug interaction network.Quantitative biology (Beijing, China) · 2026Review
- UniSyn: a multi-modal framework with knowledge transfer for anti-cancer drug synergy prediction.Genome biology · 2026Article
- Combinations of Favipiravir with Doxycycline, Azithromycin or Ivermectin Exert Synergistic Effects Against Influenza A H3N2 Virus Replication.Pathogens (Basel, Switzerland) · 2026Article
- Review
- Screening of the Pandemic Response Box Library Identified CRM1/XPO1 as an Anti-Mammarenavirus Druggable Target.Viruses · 2026Article
- Effective combinatorial antifungal therapy using a host defense peptide mimic that self-assembles into delivery micelles.Nature biotechnology · 2026Article
- A new use of Agrobacterium plant growth regulator genes for plant bioengineering.Frontiers in plant science · 2026Article
- Gut microbiome functional pathways outperform taxonomic profiles in predicting immune checkpoint inhibitor response in non-small cell lung cancer: an interpretable machine learning approach with SHAP.Frontiers in immunology · 2026Article
- VIP-OT: Dissecting Single-Cell Biochemical State Dynamics under Perturbation via Vibrational Painting and Optimal Transport.bioRxiv : the preprint server for biology · 2025Article
- Microbial Product Cocktails for Personalized Cancer Immunotherapy.Nature communications · 2025Article
- SynergyImage: image-based model for drug combinations synergy score prediction.BMC bioinformatics · 2025Article
359 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Drug combinations are a promising strategy to overcome the compensatory mechanisms and unwanted off-target effects that limit the utility of many potential drugs. However, enthusiasm for this approach is tempered by concerns that the therapeutic synergy of a combination will be accompanied by synergistic side effects. Using large scale simulations of bacterial metabolism and 94,110 multi-dose experiments relevant to diverse diseases, we provide evidence that synergistic drug combinations are generally more specific to particular cellular contexts than are single agent activities. We highlight six combinations whose selective synergy depends on multitarget drug activity. For one anti-inflammatory example, we show how such selectivity is achieved through differential expression of the drugs' targets in cell types associated with therapeutic, but not toxic, effects and validate its therapeutic relevance in a rat model of asthma. The context specificity of synergistic combinations creates many opportunities for therapeutically relevant selectivity and enables improved control of complex biological systems.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.