ArticlePloS one2014
Synergistic and antagonistic drug combinations depend on network topology.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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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.
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Who cites it
57 citing papers in PubMed, 141 citations in OpenAlex.
- A Machine Learning Approach for Predicting Synergism of Mixtures of Compounds in Treating Cancers.International journal of molecular sciences · 2026Article
- Accurate prediction of synergistic drug combination using a multi-source information fusion framework.BMC biology · 2025Article
- Computational frameworks transform antagonism to synergy in optimizing combination therapies.NPJ digital medicine · 2025Review
- MD-Syn: synergistic drug combination prediction based on a multidimensional feature fusion method and attention mechanisms.Frontiers in pharmacology · 2025Article
- Investigation of synergistic interaction of sinensetin, eupatorin, and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone in vasodilation efficacy.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Automated and miniaturized screening of antibiotic combinationsActa pharmaceutica Sinica. B · 2024Article
- Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs.Scientific reports · 2024Article
- Synergistic effect of a nonsteroidal anti-inflammatory drug in combination with topotecan on small cell lung cancer cells.Molecular biology reports · 2024Article
- Review of Predicting Synergistic Drug Combinations.Life (Basel, Switzerland) · 2023Review
- Interpreting the Mechanism of Synergism for Drug Combinations Using Attention-Based Hierarchical Graph Pooling.Cancers · 2023Article
- Predicting anti-cancer drug combination responses with a temporal cell state network model.PLoS computational biology · 2023Article
- Mechanistic model of MAPK signaling reveals how allostery and rewiring contribute to drug resistance.Molecular systems biology · 2023Article
- A Synergistic pH-Responsive Serum Albumin-Based Drug Delivery System Loaded with Doxorubicin and Pentacyclic Triterpene Betulinic Acid for Potential Treatment of NSCLC.Biotech (Basel (Switzerland)) · 2023Article
- Lipid metabolism as a target for cancer drug resistance: progress and prospects.Frontiers in pharmacology · 2023Review
- Fine tuning a logical model of cancer cells to predict drug synergies: combining manual curation and automated parameterization.Frontiers in systems biology · 2023Article
- Extraction, phytochemical characterization and anti-cancer mechanism of Haritaki churna: An ayurvedic formulation.PloS one · 2023Article
- Graph representation learning in biomedicine and healthcare.Nature biomedical engineering · 2022Review
- The MEK1/2 Inhibitor ATR-002 (Zapnometinib) Synergistically Potentiates the Antiviral Effect of Direct-Acting Anti-SARS-CoV-2 Drugs.Pharmaceutics · 2022Article
- Review
- Artificial intelligence and machine learning methods in predicting anti-cancer drug combination effects.Briefings in bioinformatics · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Drug combinations may exhibit synergistic or antagonistic effects. Rational design of synergistic drug combinations remains a challenge despite active experimental and computational efforts. Because drugs manifest their action via their targets, the effects of drug combinations should depend on the interaction of their targets in a network manner. We therefore modeled the effects of drug combinations along with their targets interacting in a network, trying to elucidate the relationships between the network topology involving drug targets and drug combination effects. We used three-node enzymatic networks with various topologies and parameters to study two-drug combinations. These networks can be simplifications of more complex networks involving drug targets, or closely connected target networks themselves. We found that the effects of most of the combinations were not sensitive to parameter variation, indicating that drug combinational effects largely depend on network topology. We then identified and analyzed consistent synergistic or antagonistic drug combination motifs. Synergistic motifs encompass a diverse range of patterns, including both serial and parallel combinations, while antagonistic combinations are relatively less common and homogenous, mostly composed of a positive feedback loop and a downstream link. Overall our study indicated that designing novel synergistic drug combinations based on network topology could be promising, and the motifs we identified could be a useful catalog for rational drug combination design in enzymatic systems.
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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.