DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephritis — screening already-approved drugs against its 36-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNephritis maps to a 36-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for nephritis is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
myotubularin related protein 2 (MTMR2) — MTMR2 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet butanoyloxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1ZSQ · 1.82 Å · ligand 2-(BUTANOYLOXY)-1-{[(HYDROXY{[2,3,4,6-TETRAHYDROXY-5-(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL)OXY]METHYL}ETHYL
BUTANOATE (PIB). Experimental structure, not a prediction.
What the evidence adds up to
In three mouse models of lupus nephritis (NZB/W F1, NZM2410, NZW/BXSB), 263 genes were regulated in all three strains, covering immune infiltration, complement activation, cytokine signalling, tissue remodelling and hypoxia. STAT3 was the top transcription factor, with binding sites in 60 of those 263 genes. Proliferative nephritis strains shared a macrophage and dendritic cell activation signature; NZB/W and NZM2410 shared a mitochondrial dysfunction signature. NZB/W mice had dominant T cell and plasma cell signatures with lymphoid aggregates and regulatory T cell infiltrates. NZW/BXSB showed tubular regeneration; NZM2410 had the most metabolic stress and lost nephrin, indicating podocyte loss. The authors concluded that shared inflammatory mechanisms exist but the heterogeneity of effector mechanisms suggests biopsy-based individualised therapy might be needed.
A 74-year-old woman developed acute renal failure and granulomatous interstitial nephritis attributed to hydrochlorothiazide/amiloride. After stopping the drug, renal function improved but not significantly. Around 20 months after prednisone was given, renal function stabilised with moderate renal insufficiency. No other cases or larger series were reported in that paper.
Two cases of nephritis following varicella were described in 1910, adding to a small number of previously published accounts. The author noted that varicella is usually mild and free from serious dangers, but complications such as nephritis occasionally occur. No treatment data or outcomes beyond the case descriptions were provided.
A 2022 study on dogs reported that combined use of cyprinol-500, furosemide, galavit and tavegil produced high therapeutic efficiency in treating canine nephritis, based on clinical, haematological, blood biochemical and urine indices. No human data, sample sizes, or survival figures were given. A 1966 review stated that no specific therapy for chronic nephritis had been established and that other treatable lesions should be ruled out first; it mentioned an experimental therapy for chronic glomerulonephritis that showed promise but gave no numbers or results.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2013 · 51 citations · open access
Comparative Transcriptional Profiling of 3 Murine Models of SLE Nephritis Reveals Both Unique and Shared Regulatory Networks
AbstractOBJECTIVE: To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease. METHODS: Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR. RESULTS: 955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss. CONCLUSIONS: These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune-mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis.
American Journal of Nephrology · 1995 · 21 citations
Granulomatous Interstitial Nephritis Associated with Hydrochlorothiazide/Amiloride
AbstractA 74-year-old woman developed acute renal failure and granulomatous interstitial nephritis associated with hydrochlorothiazide/amiloride. On stopping the drug the renal function improved, but not significantly. Around 20 months after prednisone administration, the renal function had stabilized, with a moderate degree of renal insufficiency. The case is discussed, and some aspects of acute interstitial nephritis induced by diuretics are briefly reviewed.
AbstractThe rarity of published accounts of nephritis complicating or following an attack of varicella indicates either that the associated conditions are infrequently encountered or that such cases are not reported by those observing them. It is well known that varicella is, in the majority of instances, a mild disease and free from serious dangers but occasionally the disease may be unusually severe or a complication or complications may lead to unfortunate results. When such complications are encountered it seems well to publish the account of the cases that others may profit. Among the rare complications of varicella is nephritis. Henoch<sup>1</sup>first called the attention of the profession to this complication of the disease and published the accounts of four cases studied by him. Von Jurgensen,<sup>2</sup>Brunner,<sup>3</sup>Rille,<sup>4</sup>Dillon Brown,<sup>5</sup>Hogyes,<sup>6</sup>Janssen<sup>7</sup>and Oppenheim<sup>8</sup>have reported similar cases. I have had the opportunity of studying two cases which exhibited well-marked nephritis
AbstractThe research has been conducted with the aim of developing efficient way for nephritis treatment in dogs. After making diagnosis based on the results of clinical, hematological and blood biochemical indices, as well as those of urine research, the treatment was organized per appropriate patterns. The combined application of cyprinol-500, furosemide, galavit and tavegil with antibacterial, diuretic, immuno-stimulating, antihistamine effect, has ensured high therapeutic efficiency in the treatment of dogs’ nephritis.
AbstractA specific therapy for chronic nephritis has not as yet been established, and it is therefore important that other treatable lesions be ruled out before a diagnosis of nephritis is accepted. Hypocalcemia, therapeutic agents to relieve or control bone disease, nitrogen imbalance, and hypertension are discussed. A specific therapy for chronic glomerulonephritis is suggested which, although still in experimental stages, shows great promise.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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