ArticleDiabetes2021
Connectivity Mapping Identifies BI-2536 as a Potential Drug to Treat Diabetic Kidney Disease.
Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Tubulointerstitial inflammation in glomerular diseases: mechanistic pathways, prognostic value, and translational therapeutic targets.Renal failure · 2026Review
- Transcriptome combined with single-cell data to construct a prognostic model for glycosylation-related genes in osteosarcoma.Discover oncology · 2026Article
- Mild and reversible nephrotoxicity following repeated administration of damnacanthal in nude mice.Toxicology reports · 2025Article
- Polo-like kinase2 regulates renal tubulointerstitial fibrosis via notch signaling pathway in diabetic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- WebCMap: an R package for high-throughput connectivity analysis within the CMap framework.Bioinformatics advances · 2025Article
- Mesangial Cells in Diabetic Kidney Disease: From Mechanisms to Therapeutic Implications.International journal of biological sciences · 2025Review
- A polo-like kinase 1 inhibitor enhances erastin sensitivity in head and neck squamous cell carcinoma cells in vitro.Cancer chemotherapy and pharmacology · 2024Article
- Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis.Cell death & disease · 2023Article
- Mycophenolic acid directly protects podocytes by preserving the actin cytoskeleton and increasing cell survival.Scientific reports · 2023Article
- DNA Methylation-Specific Analysis of G Protein-Coupled Receptor-Related Genes in Pan-Cancer.Genes · 2022Article
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
- Immunoprognostic model of lung adenocarcinoma and screening of sensitive drugs.Scientific reports · 2022Article
- Identification of small molecules as novel anti-adipogenic compounds based on Connectivity Map.Frontiers in endocrinology · 2022Article
- Inhibition of HDAC6 With CAY10603 Ameliorates Diabetic Kidney Disease by Suppressing NLRP3 Inflammasome.Frontiers in pharmacology · 2022Article
- Gene Expression as a Guide to the Development of Novel Therapies in Primary Glomerular Diseases.Journal of clinical medicine · 2021Article
- Staying Connected: Transcriptomics in the Search for Novel Diabetic Kidney Disease Treatments.Diabetes · 2021Article
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10 authors at 3 institutions in 2 countries.
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Abstract
Diabetic kidney disease (DKD) remains the most common cause of kidney failure, and the treatment options are insufficient. Here, we used a connectivity mapping approach to first collect 15 gene expression signatures from 11 DKD-related published independent studies. Then, by querying the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 data set, we identified drugs and other bioactive small molecules that are predicted to reverse these gene signatures in the diabetic kidney. Among the top consensus candidates, we selected a PLK1 inhibitor (BI-2536) for further experimental validation. We found that PLK1 expression was increased in the glomeruli of both human and mouse diabetic kidneys and localized largely in mesangial cells. We also found that BI-2536 inhibited mesangial cell proliferation and extracellular matrix in vitro and ameliorated proteinuria and kidney injury in DKD mice. Further pathway analysis of the genes predicted to be reversed by the PLK1 inhibitor was of members of the TNF-α/NF-κB, JAK/STAT, and TGF-β/Smad3 pathways. In vitro, either BI-2536 treatment or knockdown of PLK1 dampened the NF-κB and Smad3 signal transduction and transcriptional activation. Together, these results suggest that the PLK1 inhibitor BI-2536 should be further investigated as a novel therapy for DKD.
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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.