DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for lupus nephritis — screening already-approved drugs against its 21-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLupus nephritis maps to a 21-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
approvedCyclosporineApproved drug
Structures already discussed alongside lupus nephritis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
FKBP prolyl isomerase 1A (FKBP1A) — FKBP1A is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has (4~{s},5~{r},6~{z},9~{s},10~{s},12~{e})-16-(ethylamino)-4,5-dimethyl-9,10,18-tris(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione bound in it, shown as sticks.
Loading structure…
helix sheet 4~{s},5~{r},6~{z},9~{s},10~{s},12~{e}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I1S · 1.52 Å · ligand (4~{S},5~{R},6~{Z},9~{S},10~{S},12~{E})-16-(ethylamino)-4,5-dimethyl-9,10,18-tris(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione (E26). Experimental structure, not a prediction.
What the evidence adds up to
Lupus nephritis occurs in as many as half of patients with systemic lupus erythematosus and is a major predictor of morbidity and mortality. Before the last decade, treatment was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, prescribed regardless of patient demographics or prior toxicities. Over the last decade, new immunomodulatory agents emerged as effective induction and maintenance therapies, allowing physicians to individualise regimens to maximise clinical benefit and minimise adverse events. Randomised controlled trials have demonstrated the efficacy of these new regimens.
Despite extensive clinical and translational research, lupus nephritis remains a kidney disease with significant unmet medical needs. These include predicting individual risk for LN, identifying the best therapeutic option for a given patient, distinguishing chronic kidney damage from active immunologic injury, and developing efficient treatments with acceptable or no side effects. The design of randomised clinical trials also needs improvement so that effective drugs can demonstrate efficacy.
Current treatment is based largely upon hormones and immunosuppressants associated with adverse effects such as easy relapse and easy infection. In recent years, researchers have identified a variety of biologic agents capable of enhancing the efficacy of traditional treatment regimens while minimising drug side effects. A 2024 review summarised the latest research on these novel biologic therapeutic agents for LN.
What is still missing are trial designs that can reliably show efficacy for new drugs, methods to predict individual patient risk and match patients to the best therapy, and the ability to distinguish active immunologic injury from chronic damage without relying on kidney biopsy. The underlying reasons for these unmet needs have been discussed but not yet resolved.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Lupus · 2000 · 75 citations
Cyclosporine for lupus membranous nephritis:experience with ten patients and review of the literature
AbstractOBJECTIVES: The treatment of lupus membranous nephritis (LMN), a lupus subset that carries a high morbidity, is unsatisfactory. We report our experience in treating LMN with the immunosuppressive drug cyclosporine (CYS). METHODS: We treated 10 patients with systemic lupus erythematosus fulfilling ACR criteria with CYS for at least 12 months and followed renal function, serologic activity and SLEDAI scores. PATIENT CHARACTERISTICS: 8 females, 2 males, 50% Caucasian, mean age 37.3 y (range 22-48), disease duration 108.7 months (range 16-216), nephritis duration 35.5 months (range 12-59), date of biopsy to date of starting treatment 10.7 months (range 0-90). The patients were started on CYS with a mean dose of 3.8 mg/kg (range 2.2-6) and followed for a mean duration of 24.8 months (range 12-59). A Medline search identified all patients with lupus who were given CYS or had LMN in articles from 1966-1999. RESULTS: Proteinuria improved from a baseline mean of 5,588mg/24h (range 2,712-11,055) to 1,404 mg/24 h (range < 150-2,652). Serum albumin increased from a baseline mean of 2.8 g/100 ml (range 1.31-3.8) to a mean of 3.9 g/100 ml (range 3-4.5) at last follow-up. There was no significant change in lupus activity as measured by SLEDAI. Nephrotoxicity was common as evidenced by an increase in serum creatinine but it returned to baseline with adjustment of the dose of CYS (20% decrease in the dose of CYS for a 20% increase in serum creatinine). More antihypertensive medications were required to control the blood pressure in these ten patients at the end of the study compared to the onset (total number= 13 versus 6). CONCLUSION: Proteinuria and serum albumin improved in all patients on CYS. A literature review is consistent with this. Controlled studies of the use of CYS for membranous lupus nephritis would be useful.
Current Opinion in Nephrology & Hypertension · 2013 · 39 citations
Update on the treatment of lupus nephritis
AbstractPURPOSE OF REVIEW: Lupus nephritis occurs in as many as half of patients presenting with systemic lupus erythematosus and is a major predictor of morbidity and mortality in this patient population. Prior to the last decade, the treatment of lupus nephritis was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, and this therapy was broadly prescribed regardless of patient demographics, clinical presentation, or prior toxicities. RECENT FINDINGS: Over the last decade, new immunomodulatory agents have emerged as effective induction and maintenance therapies in lupus nephritis. With these options, physicians are able to individualize the treatment regimens in an attempt to maximize clinical benefit and minimize adverse events. Moreover, the influence of patient demographics on disease severity and response to treatment has come to the forefront. SUMMARY: Here, we review the recent progress made in the therapy of lupus nephritis with a focus on the randomized controlled trials which have demonstrated the efficacy of these new treatment regimens.
AbstractApproaches to treatment of lupus nephritis have been complicated by controversies in the definitions of the types of renal histology, the relevance of immunological and renal monitoring techniques as therapeutic guidelines, and lack of definitive clinical trials. It is suggested that demonstration of the efficacy of various therapeutic agents in clinical trials may be identified earlier by renal histological changes and/or assessment of drug toxicity compared to the time required for differences based on renal functional changes to emerge as ultimate measures of outcome.
Unmet medical needs in lupus nephritis: solutions through evidence-based, personalized medicine
AbstractLupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy. This review discusses the underlying reasons for these unmet medical needs and options of how to overcome them in the future.
Portuguese Journal of Nephrology & Hypertension · 2020 · 3 citations · open access
Treatment of lupus nephritis – past, present and (near) future
AbstractLupus nephritis is one of the best -studied SLE complications. The reasons are two -fold: 1) the morbidity and mortality are increased in SLE patients with renal involvement; 2) kidney biopsies, as opposed to serum autoantibodies, allow for direct visualization of active and chronic damage to tissues. It is thus no surprise that a histomorphological classification emerged in 1964 3 , based solely on light microscopy. This first attempt classified patients into 3 groups: lupus glomerulitis; active lupus glomerulonephritis and membranous lupus glomerulonephritis. Few changes were made until the 2004 joint World Health Organization and ISN/RPS (International Society of Nephrology / Renal Pathology Society) classification, which is still used to this date (Table
DOAJ (DOAJ: Directory of Open Access Journals) · 2024 · 0 citations · open access
Research advances of novel biologic therapeutic agents for lupus nephritis
AbstractLupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus (SLE). Current treatment of LN is based largely upon hormones and immunosuppressants associated with such adverse effects as easy relapse and easy infection. In recent years, researchers have identified a variety of biologic agents capable of enhancing the efficacy of traditional treatment regimens while minimizing drug side effects. This review summarized the latest researches of novel biologic therapeutic agents for LN.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
