ArticlePharmaceuticals (Basel, Switzerland)2018
Proximal Pathway Enrichment Analysis for Targeting Comorbid Diseases via Network Endopharmacology.
Article in Pharmaceuticals (Basel, Switzerland), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.Nature aging · 2021Trial
- Integrating Divergence-Based Proteomic Analysis and Directed Network Diffusion to Characterize Diagnosis-Anchored Molecular Variability at the Metabolic Syndrome-Migraine Interface.International journal of molecular sciences · 2026Article
- Integrated network pharmacology andFrontiers in immunology · 2026Article
- Advances in Computational Drug Repurposing, Driver Genes, and Therapeutics in Lung Adenocarcinoma.Biomolecules · 2025Review
- One path, two solutions: Network-based analysis identifies targetable pathways for the treatment of comorbid type II diabetes and neuropsychiatric disorders.Computational and structural biotechnology journal · 2024Article
- Phenotypic drug discovery: a case for thymosin alpha-1.Frontiers in medicine · 2024Review
- Turning Microbial AhR Agonists into Therapeutic Agents via Drug Delivery Systems.Pharmaceutics · 2023Review
- Re-Addressing Dementia by Network Medicine and Mechanism-Based Molecular Endotypes.Journal of Alzheimer's disease : JAD · 2023Article
- A network paradigm predicts drug synergistic effects using downstream protein-protein interactions.CPT: pharmacometrics & systems pharmacology · 2022Article
- Visualizing novel connections and genetic similarities across diseases using a network-medicine based approach.Scientific reports · 2022Article
- From random to predictive: a context-specific interaction framework improves selection of drug protein-protein interactions for unknown drug pathways.Integrative biology : quantitative biosciences from nano to macro · 2022Article
- Reconciling multiple connectivity scores for drug repurposing.Briefings in bioinformatics · 2021Article
- The Complex Structure of the Pharmacological Drug-Disease Network.Entropy (Basel, Switzerland) · 2021Article
- Degree Adjusted Large-Scale Network Analysis Reveals Novel Putative Metabolic Disease Genes.Biology · 2021Article
- NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype.PLoS biology · 2020Article
- Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients.Nature communications · 2020Article
- The Interplay between Diabetes and Alzheimer's Disease-In the Hunt for Biomarkers.International journal of molecular sciences · 2020Review
- Network Medicine Approach for Analysis of Alzheimer's Disease Gene Expression Data.International journal of molecular sciences · 2020Article
- Article
- From single drug targets to synergistic network pharmacology in ischemic stroke.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The past decades have witnessed a paradigm shift from the traditional drug discovery shaped around the idea of “one target, one disease” to polypharmacology (multiple targets, one disease). Given the lack of clear-cut boundaries across disease (endo)phenotypes and genetic heterogeneity across patients, a natural extension to the current polypharmacology paradigm is to target common biological pathways involved in diseases via endopharmacology (multiple targets, multiple diseases). In this study, we present proximal pathway enrichment analysis (PxEA) for pinpointing drugs that target common disease pathways towards network endopharmacology. PxEA uses the topology information of the network of interactions between disease genes, pathway genes, drug targets and other proteins to rank drugs by their interactome-based proximity to pathways shared across multiple diseases, providing unprecedented drug repurposing opportunities. Using PxEA, we show that many drugs indicated for autoimmune disorders are not necessarily specific to the condition of interest, but rather target the common biological pathways across these diseases. Finally, we provide high scoring drug repurposing candidates that can target common mechanisms involved in type 2 diabetes and Alzheimer’s disease, two conditions that have recently gained attention due to the increased comorbidity among patients.
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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.