Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32913274", "kind": "science-record", "revision": 6, "content_hash": "sha256:06d391fcc2b8c54ef6946032cb0d460d1b43c2af77d34d96ca287db96b1a48c0", "created_at": "2026-11-01T15:41:10Z", "updated_at": "2026-11-01T21:23:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease.", "doi": "10.1038/s41598-020-71950-7", "pmid": "32913274", "authors": ["Julie Klein", "Cécile Caubet", "Mylène Camus", "Manousos Makridakis", "Colette Denis", "Marion Gilet", "Guylène Feuillet", "Simon Rascalou", "Eric Neau", "Luc Garrigues", "Olivier Thillaye du Boullay", "Harald Mischak", "Bernard Monsarrat", "Odile Burlet-Schiltz", "Antonia Vlahou", "Jean Sébastien Saulnier-Blache", "Jean-Loup Bascands", "Joost P Schanstra"], "journal": "Scientific reports", "year": 2020, "abstract": "While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). The raw data are publicly available via ProteomeXchange with identifier PXD018728. We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs's signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthenolide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs's signature. Oral treatment of 2 months old Ins2Akita mice with dimethylaminoparthenolide (DMAPT, a water-soluble analogue of parthenolide) for two months at 10 mg/kg/d by gavage significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach, we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD.", "claims": [{"id": "claim-method", "statement": "Proteins with a p value of less than 0.05 (T-test) were considered as significantly varying between two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32913274", "locator": "sections[22] \"Data processing and statistical analysis\" paragraph 2", "quote": "Proteins with a p value of less than 0.05 (T-test) were considered as significantly varying between two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics raw data have been deposited to the ProteomeXchange Consortium via the PRIDE40 partner repository with the dataset identifier PXD018728.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32913274", "locator": "sections[23] \"Proteomic data availability\" paragraph 2", "quote": "The mass spectrometry proteomics raw data have been deposited to the ProteomeXchange Consortium via the PRIDE40 partner repository with the dataset identifier PXD018728."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32913274"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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ALB, ATP2A2, ATP2B2, ABCA9, SLC6A6, SLC9A1, SLC5A9, ATP11C"], ["Folding of actin by CCT/TriC", "3.55E−6", "CCT4, CCT5, CCT3, CCT7"], ["A subgroup of genes regulated by MYC-version 1 (v1)", "5.53E−6", "CCT4, CCT5, CCT3, CCT7, PSMD7, HSPD1, RACK1, SF3B3"], ["Protein localization", "1.94E−5", "HSPD1, PMPCB, AMACR, ALDH3A2, DECR2, LDHD, ATAD1"], ["Formation of tubulin folding intermediates by CCT/TriC", "8.21E−5", "CCT4, CCT5, CCT3, CCT7"], ["Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding", "1.91E−4", "CCT4, CCT5, CCT3, CCT7"], ["Association of TriC/CCT with target proteins during biosynthesis", "3.32E−4", "CCT4, CCT5, CCT3, CCT7"], ["Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding", "4.00E−04", "CCT4, CCT5, CCT3, CCT7"], ["Asparagine N-linked glycosylation", "6.35E−4", "OS9, DYNC1H1, SPTAN1, DDOST, SPTBN1, DCTN5, MIA2"], ["Neutrophil degranulation", "1.14E−3", "DYNC1H1, SPTAN1, DDOST, PSMD7, AP2A2, PSMD12, CD36, COMMD9"]], "row_count": 11, 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["Pyridoxine", "0", "4", "− 0.686", "–", "–", "0", "Vitamin B6"], ["Antazoline", "− 0.317", "4", "− 0.67", "0.02668", "0.0315", "50", "Histamine receptor antagonist"], ["Puromycin", "− 0.154", "4", "− 0.657", "–", "–", "25", "Protein synthesis inhibitor"], ["Cisapride", "− 0.147", "4", "− 0.646", "–", "–", "25", "Serotonin receptor agonist"], ["Nifenazone", "− 0.364", "5", "− 0.64", "0.01544", "0.0132", "60", "Analgesic"], ["Emetine", "0", "4", "− 0.633", "–", "–", "0", "Protein synthesis inhibitor"], ["Cinchonine", "− 0.427", "4", "− 0.631", "0.04538", "0.1975", "75", "P-glycoprotein inhibitor"], ["Piperacetazine", "− 0.283", "4", "− 0.629", "0.04629", "0.0438", "50", "Dopamine receptor antagonist"], ["Natamycin", "0", "4", "− 0.628", "–", "–", "0", "Antibiotic"]], "row_count": 21, "column_count": 8, "numeric_cells": 100, "header_rows": 1, "locator": "section[9]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:32913274:4", "role": "table", "format": "jats-table", "media_type": 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