DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrotic syndrome — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNephrotic syndrome maps to a 46-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 nephrotic syndrome 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
nuclear receptor subfamily 3 group C member 2 (NR3C2) — NR3C2 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 2,2-difluoro-3-hydroxypropyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4PF3 · 1.1 Å · ligand 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (HFN). Experimental structure, not a prediction.
What the evidence adds up to
A 2017 literature review notes that treatment outcomes for primary nephrotic syndrome have changed with new therapy technologies, and that monoclonal antibodies represent an immediate opportunity for new treatment approaches. The review does not provide specific efficacy data.
A 2024 retrospective multicentre cohort study of 121 children with idiopathic nephrotic syndrome (median age 4.5 years, median follow-up 3.7 years) found that the time to a subsequent relapse after diagnosis of frequent relapses or steroid-dependent nephrotic syndrome was the only significant predictor of needing a steroid-sparing agent (adjusted hazard ratio 2.26, 95% CI 1.26–4.05). Children who relapsed within three months of that diagnosis required steroid-sparing agents earlier (log-rank p = 0.005), had more relapses, more steroid-related adverse events, and were more likely to develop steroid dependency. The authors call for prospective research to confirm this.
A 2022 Bayesian network analysis of immunosuppressive agents for refractory nephrotic syndrome in adults states that some patients are difficult to cure due to frequent recurrence and can face unpredictable complications and life-threatening side effects from steroids and immunosuppressants. The abstract does not report remission rates, response rates, or sample sizes, and does not name any specific drug that showed efficacy.
What is still missing: prospective trials that confirm the timing-of-relapse predictor in children, and for adults with refractory nephrotic syndrome, any clear evidence from randomised controlled trials that identifies which immunosuppressive agent, if any, produces acceptable remission rates with tolerable adverse effects. Patient stratification by genetic cause or relapse timing is not yet validated for routine clinical decisions.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Pharmacotherapy · 2012 · 17 citations
Sunitinib- and Sorafenib-lnduced Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor
AbstractOBJECTIVE: To report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy. CASE SUMMARY: A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved. DISCUSSION: Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development. CONCLUSIONS: The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.
Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · 2017 · 13 citations · open access
NEPHROTIC SYNDROME: PAST, PRESENT AND FUTURE
AbstractThis literature review is focused to change our ideas about the etiology, pathogenesis and treatment tactics of the nephrotic syndrome in recent decades. The change in the treatment outcomes of the primary nephrotic syndrome in connection with the emergence of new therapy technologies, is shown. Features of the course, examination and therapy of congenital and infantile nephrotic syndrome and the possibility of the debut of a nephrotic syndrome associated with various gene mutations and at an older age are presented. Principal differences in diagnostic and therapeutic approaches are accentuated depending on the cause of the development of the disease. Modern syndromological and pathogenetic methods of therapy of primary nephrotic syndrome are presented, and the immediate opportunities for the introduction of new treatment technologies based on the use of monoclonal antibodies, are shown.
Dasatinib Induced Reversible Nephrotic Range Proteinuria Occurs More Frequently Compared to Other Tyrosine Kinase Inhibitors in the Treatment of Chronic Myeloid Leukemia
AbstractAbstract Introduction: Dasatinib is an oral inhibitor of Abl and Src family of kinases. Dasatinib can cause a pleural effusion in 14% to 30% of patients as well as pulmonary arterial hypertension. Its mechanism is not fully elucidated although vascular endothelial growth factor (VEGF)-mediated mechanism has been proposed. In the literature, there are sporadic case reports of dasatinib-induced proteinuria/nephrotic syndrome. It is also suggested that dasatinib-induced kidney injury involves the interruption of VEGF signaling pathway. In the present study, we present a series of 6 patients, who developed nephrotic-range proteinuria while on dasatinib therapy that resolved after switch to other TKIs or discontinuation. Also, we have analyzed the risk of TKI-associated proteinuria according to the TKI subtype in 256 CML patients having available results of urine protein level. Patients and Methods: A total of 256 patients with CML on TKIs, with available urine testing were reviewed. TKI therapy was as follows: Imatinib (n=147), dasatinib (n=67), nilotinib (n=13), ponatinib (n=13) and bosutinib (n=16). First, we have reviwed spot urinalysis result for proteinuria screening, and further reviewed in detail the result of 24-hour urine protein measurement. If proteinuria is detected, we had in-depth chart review on the case to exclude other causes of proteinuria such as diabetes, renal failure, urinary tract infecion or urinary tract malignancies, etc. After excluding other causes of proteinuria, we have calculated the incidence rate of proteinuria using 1,000 person-year considering duration of exposure to TKI therapy. Results: With median duration of 35 months of dasatinib therapy, 6 patients (8.9%) developed nephrotic range proteinuria, after excluding other secondary causes of proteinuria. All received dasatinib as 2nd line following Imatinib front line therapy. Out of 6 patients with proteinuria, 4 patients developed pleural effusion prior to the development of proteinuria. All of them showed optimal molecular response to dasatinib therapy at the time of proteinuria development including MR4.5 (n=4), MR4.0 (n=1) or MMR (n=1). One patient underwent renal biopsy which showed chronic glomerular endothelial cell injury and thin basement membrane nephropathy, consistent with finding of minimal change disease. All 6 cases had discontinued (n=3) or switched to other TKI therapy (imatinib n=1; botutinib n=1; nilotinib n=1) with complete resolution of proteinuria. In the 3 patients who had MR4.5 or deeper response when dasatinib was discontinued due to proteinuria, one lost MMR after 3 months, one maintained MMR (+13 months), and another without losing undetectable transcript level (+21 months). The incidence rate of TKI-associated proteinuria was analyzed according to the TKI subtype in 256 CML patients. Median follow-up duration was 31 months for 35 months for dasatinib (1-105 months), imatinib (1-172 months), 27 months for nilotinib (1-63 months), 5 months for bosutinib (1-22 months), and 1 month for ponatinib (1-14 months), respectively. The exposure year was 201.8 years in dasatinib (n=67), 523.2 years in imatinib (n=147), 31.4 years in nilotinib (n=13), 6.1 years in bosutinib (n=16) and 1.4 years in ponatinib (n=13). The incidence rate of proteinuria in dasatinib treated group was calculated as 29/1,000 person-year, while it was 0 in imatinib, nilotinib, bosutinib, ponatinib-treated group, respectively due to no case confirmed to have proteinuria after excluding secondary causes of proteinuria (Fisher's exact test p Conclusion: Development of nephrotic range proteinuria can be a toxicity from dasatinib therapy in CML treatment. Incidence rate is unexpectedly high at 29/1,000 person-year while there are no cases of nephrotic range proteinuria with exposure to other TKIs. All the proteinuria events were reversed completely after discontinuation/switch of dasatinib. Medical attention is to be paid for this unusual toxicity related to dasatinib therapy. Further study is strongly warranted to reach a clear conclusion for the incidence of this toxicity in a larger cohort. Disclosures Kim: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy; Pfizer: Consultancy.
Timing of relapse as a key indicator of steroid-sparing requirements in childhood idiopathic nephrotic syndrome
AbstractBACKGROUND: Managing children with frequent relapses or steroid-dependent nephrotic syndrome poses challenges due to recurrent relapses necessitating prolonged steroid exposure, thus increasing susceptibility to long-term complications. Identifying those at risk of poor response to steroid therapy may be helpful to guide timely intervention with steroid-sparing agents. This study aimed to identify factors associated with steroid-sparing agent needs in children with frequent relapses or steroid-dependent nephrotic syndrome. METHODS: A retrospective multicenter cohort study was conducted by reviewing the medical records of children with idiopathic nephrotic syndrome treated between 2006 and 2023. Cox proportional regression analyzed prognostic factors for steroid-sparing agent requirements in children with frequent relapses or steroid-dependent nephrotic syndrome. The time-to-event analysis utilizing the Kaplan-Meier estimate examined the proportion of children needing steroid-sparing agents after diagnosis. RESULTS: Medical records of 121 children (85 males) diagnosed with idiopathic nephrotic syndrome at a median age of 4.5 years (range 1.3-12.8) were reviewed over a median follow-up of 3.7 years (range 1.0-15.0). Time to subsequent relapse post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis (at 3-month threshold) emerged as the sole significant predictor of steroid-sparing agent requirement, adjusted hazard ratio (aHR) = 2.26, 95% confidence interval (CI) 1.26-4.05. Kaplan-Meier analysis indicated that an earlier first relapse (< 3 months) led to earlier steroid-sparing agent requirement (log-rank p = 0.005). Children who relapsed within 3 months post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis exhibited a higher frequency of relapses, a greater incidence of steroid-related adverse events, and were more likely to develop steroid dependency. CONCLUSIONS: Early subsequent relapse following diagnosis of frequent relapses or steroid-dependent nephrotic syndrome was linked to earlier requirement of steroid-sparing agent therapy. Further prospective research is necessary to confirm this observation.
Kidney International Reports · 2022 · 0 citations · open access
POS-218 Immunosuppressive Agents for Refractory Nephrotic Syndrome in adults: A Bayesian Network Analysis
AbstractNephrotic syndrome is a common and frequently occurring disease in chronic kidney diseases. However, some patients are often difficult to cure due to frequent recurrence, and can lead to unpredictable complications, side effects of steroids and immunosuppressants, and even life-threatening. Therefore, this study aimed to clarify the efficacy and acceptability of immunosuppressive therapy at inducing remission and adverse reaction in refractory nephrotic syndrome (RNS).
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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