ArticleProceedings of the National Academy of Sciences of the United States of America2019
From single drug targets to synergistic network pharmacology in ischemic stroke.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04776499 (Clinical Evaluation in Healthy Volunteers of Potential syneRgistic Vascular Effects of PrOpylthiouracil, Riociguat, and Perphenazine a Possible STROKE Medication), which is not on this map. Cited by 118 papers, 2 of them syntheses that pooled it.
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.
Clinical Evaluation in Healthy Volunteers of Potential syneRgistic Vascular Effects of PrOpylthiouracil, Riociguat, and Perphenazine a Possible STROKE Medication
Who cites it
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 235 citations in OpenAlex.
- Neuroprotective Effects of Conditioned Medium of Mesenchymal Stem Cells (MSC-CM) as a Therapy for Ischemic Stroke Recovery: A Systematic Review.Neurochemical research · 2023Pooled it
- Un-biased housekeeping gene panel selection for high-validity gene expression analysis.Scientific reports · 2022Pooled it
- Synergistic Network Pharmacology: Preclinical Validation and Clinical Safety in Acute Ischemic Stroke.Journal of the American Heart Association · 2025Trial
- Review
- Synergistic antiviral effects of structure-guided peptides and a mutagenic base analog on SARS-CoV-2 replication.Antimicrobial agents and chemotherapy · 2026Article
- Design of permeability-optimized target-binding macrocyclesChemical science · 2026Article
- MT-ConBiFormer-GPT: multi-target molecular generation for low-data drug discovery via a contrastive BiFormer-GPT architecture and curriculum learning with cross-domain generalization.Briefings in bioinformatics · 2026Article
- Network Pharmacology and Molecular Docking-Based Investigation of Empagliflozin's Therapeutic Potential in Chronic Kidney Disease.Life (Basel, Switzerland) · 2026Article
- Problems associated with the ATC system of drug classification.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Evaluating the Antioxidant Potential of Coumestrol in the Treatment of Tripterygium Glycoside-Induced Oligospermia in Rats and Its Potential Mechanisms.Veterinary sciences · 2026Article
- Huazhuo Decoction Contributes to Immune Homeostasis and Attenuates Neuronal Inflammation and Demyelination in a Mouse Model of Multiple Sclerosis.Journal of inflammation research · 2026Article
- Multi agent large language models for biomedical hypothesis generation in drug combination discovery.iScience · 2025Article
- A holistic view on disease-modifying aspects, comorbidities, and contemporary neuroprotective approaches.Neuroprotection (Chichester, England) · 2025Article
- Discovery of active compounds in Danshen-Chuanxiong formula for blood-brain barrier protection: a multi-parametric study using an OGD/R-induced spheroid model.Journal of natural medicines · 2025Article
- InterPAD is a database of drug-drug interaction between phytochemicals and anticancer drugs.Scientific reports · 2025Article
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Modular-Based Synergetic Mechanisms of Jasminoidin and Ursodeoxycholic Acid in Cerebral Ischemia Therapy.Biomedicines · 2025Article
- Elucidating the role of artificial intelligence in drug development from the perspective of drug-target interactions.Journal of pharmaceutical analysis · 2025Review
- Article
- A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement.Acta pharmaceutica Sinica. B · 2025Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug discovery faces an efficacy crisis to which ineffective mainly single-target and symptom-based rather than mechanistic approaches have contributed. We here explore a mechanism-based disease definition for network pharmacology. Beginning with a primary causal target, we extend this to a second using guilt-by-association analysis. We then validate our prediction and explore synergy using both cellular in vitro and mouse in vivo models. As a disease model we chose ischemic stroke, one of the highest unmet medical need indications in medicine, and reactive oxygen species forming NADPH oxidase type 4 (
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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.