ArticleEBioMedicine2020
Prioritization of novel ADPKD drug candidates from disease-stage specific gene expression profiles.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Species, cell proliferation state and oxygen partial pressure are major factors in the in vitro toxicity of repurposed potential ADPKD drugs in human and murine renal proximal tubule cells.Archives of toxicology · 2026Article
- Spatial Transcriptomics Reveals Injured Cells, Signature Genes, and Communication Patterns in the Cyst Microenvironment of Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- Inactivation of Pkd2 in adult mice results in delayed cyst formation and identifies sex as a major modifier of disease severity.Kidney international · 2026Article
- Computational Drug Repositioning in Cardiorenal Disease: Opportunities, Challenges, and Approaches.Proteomics · 2025Article
- A Patient-Derived 3D Cyst Model of Polycystic Kidney Disease That Mimics Disease Development and Responds to Repurposing Candidates.Clinical and translational science · 2025Article
- Reprogramming of Energy Metabolism in HumanInternational journal of molecular sciences · 2024Article
- Computational drug discovery approaches identify mebendazole as a candidate treatment for autosomal dominant polycystic kidney disease.Frontiers in pharmacology · 2024Article
- Prioritized polycystic kidney disease drug targets and repurposing candidates from pre-cystic and cystic mouse Pkd2 model gene expression reversion.Molecular medicine (Cambridge, Mass.) · 2023Article
- Preclinical evaluation of tolvaptan and salsalate combination therapy in aFrontiers in molecular biosciences · 2023Article
- Effects of Suramin on Polycystic Kidney Disease in a Mouse Model of Polycystin-1 Deficiency.International journal of molecular sciences · 2022Article
- The wind of change in the management of autosomal dominant polycystic kidney disease in childhood.Pediatric nephrology (Berlin, Germany) · 2022Review
- Endocannabinoid System in Polycystic Kidney Disease.American journal of nephrology · 2022Article
- Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidneys of three Pkd1-deficient mouse models.Scientific reports · 2021Article
- Drug repurposing in autosomal dominant polycystic kidney disease: back to the future with pioglitazone.Clinical kidney journal · 2021Article
- Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD.Frontiers in medicine · 2021Review
- Autosomal dominant polycystic kidney disease and pioglitazone for its therapy: a comprehensive review with an emphasis on the molecular pathogenesis and pharmacological aspects.Molecular medicine (Cambridge, Mass.) · 2020Review
- Pathway identification through transcriptome analysis.Cellular signalling · 2020Review
- Informatics-guided drug repurposing for Autosomal Dominant Polycystic Kidney Disease (ADPKD).EBioMedicine · 2020Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAutosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common causes of end-stage renal failure, caused by mutations in PKD1 or PKD2 genes. Tolvaptan, the only drug approved for ADPKD treatment, results in serious side-effects, warranting the need for novel drugs.
methodsIn this study, we applied RNA-sequencing of Pkd1cko mice at different disease stages, and with/without drug treatment to identify genes involved in ADPKD progression that were further used to identify novel drug candidates for ADPKD. We followed an integrative computational approach using a combination of gene expression profiling, bioinformatics and cheminformatics data.
findingsWe identified 1162 genes that had a normalized expression after treating the mice with drugs proven effective in preclinical models. Intersecting these genes with target affinity profiles for clinically-approved drugs in ChEMBL, resulted in the identification of 116 drugs targeting 29 proteins, of which several are previously linked to Polycystic Kidney Disease such as Rosiglitazone. Further testing the efficacy of six candidate drugs for inhibition of cyst swelling using a human 3D-cyst assay, revealed that three of the six had cyst-growth reducing effects with limited toxicity.
interpretationOur data further establishes drug repurposing as a robust drug discovery method, with three promising drug candidates identified for ADPKD treatment (Meclofenamic Acid, Gamolenic Acid and Birinapant). Our strategy that combines multiple-omics data, can be extended for ADPKD and other diseases in the future.
fundingEuropean Union's Seventh Framework Program, Dutch Technology Foundation Stichting Technische Wetenschappen and the Dutch Kidney Foundation.
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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.