DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for Polycystic Kidney Disease — screening already-approved drugs against its 15-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePolycystic Kidney Disease maps to a 15-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
approvedEverolimusApproved drug
Structures already discussed alongside polycystic kidney disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Cytochrome P450 107G1 (RapN) — Everolimus has a real, experimentally solved structure in complex with this target (PDB 6L3A, 3.0 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet e53drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6L3A · 3.0 Å · ligand Everolimus (E53). Experimental structure, not a prediction.
What the evidence adds up to
Autosomal dominant polycystic kidney disease is the reported cause of end-stage kidney disease in 10% of patients, with an estimated global prevalence of 12.5 million cases across all ethnicities. The disease is generally linked to mutations in the PKD1 and PKD2 genes, which encode polycystin 1 and polycystin 2 proteins that form a complex regulating common cell signalling pathways. Some patients with ADPKD have no detectable pathogenic gene.
The only drug to have received regulatory approval for ADPKD patients at risk of rapid progression to kidney failure is tolvaptan, a vasopressin V2 receptor antagonist. Clinical trials have also been conducted on liksivaptan (another V2 receptor antagonist), the multi-kinase inhibitor tezevatinib, somatostatin analogues lanreotide and octreotide, the statin pravastatin, mTOR inhibitors everolimus and sirolimus, and metformin. The 2019 review of these trials does not report any of these agents as having achieved regulatory approval for ADPKD beyond tolvaptan. Surgical treatment is described as a common and effective method in clinical practice, but no specific survival or response rates are given in any of these abstracts.
The 2007 review notes that increased understanding of genetic, molecular and cellular mechanisms has laid the foundation for rational therapies, and that many animal models are available for testing. It mentions that some clinical trials were already in early phases of implementation at that time. The 2022 review frames the management of ADPKD as now existing in an era of disease-modifying treatment options, but the only disease-modifying agent it identifies as having reached regulatory approval is tolvaptan.
What remains missing from the evidence summarised here is any large-scale, randomised data showing that any drug other than tolvaptan slows progression to kidney failure in ADPKD. No abstract provides head-to-head comparisons of the various agents tested, nor does any abstract report long-term survival outcomes. The patient stratification needed to identify who benefits from which drug, and the funding for trials that compare these agents against each other or against placebo in genetically defined subgroups, are not addressed in these reviews.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Internal Medicine · 2007 · 126 citations · open access
AbstractAn increased understanding of the genetic, molecular and cellular mechanisms responsible for the development of polycystic kidney disease has laid out the foundation for the development of rational therapies. Many animal models where these therapies can be tested are currently available. This review summarizes the rationale for these treatments, the results of preclinical trials and the prospects for clinical trials, some already in early phases of implementation.
Kidney Research and Clinical Practice · 2022 · 31 citations · open access
Management of autosomal dominant polycystic kidney disease in the era of disease-modifying treatment options
AbstractAutosomal dominant polycystic kidney disease (ADPKD) is the reported etiology in 10% of end-stage kidney disease (ESKD) patients and has an estimated prevalence of 12.5 million cases worldwide across all ethnicities. There have been major advancements over the last two decades in understanding the pathogenesis and development of disease-modifying treatment options for ADPKD, culminating in regulatory approval of tolvaptan for ADPKD patients at risk of rapid progression to kidney failure. This review highlights the genetic mutations associated with ADPKD, defines patients at risk of rapid progression to ESKD, and focuses on the management of ADPKD in the era of disease-modifying agents.
Fetal and Pediatric Pathology · 1998 · 3 citations
Molecular Biology of Autosomal Dominant Polycystic Kidney Disease
AbstractAmong the prevalent human genetic disorders, human autosomal dominant polycystic kidney disease is certainly one of the most challenging, both from a clinical and a fundamental perspective. In the recent years, important progress opened novel research avenues to elucidate the genetic basis, the cellular pathophysiologic mechanisms and the molecular function of genes and proteins involved in autosomal dominant polycystic kidney disease.
Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · 2019 · 2 citations · open access
Treatment of autosomal recessive and autosomal dominant polycystic kidney disease
AbstractThe article reflects the genetic variants of polycystic kidney disease, describes the modern strategy for the treatment of polycystic kidney disease in children and adults. The authors present the results of clinical trials of vasopressin V2 receptor antagonists (tolvaptan, liksivaptan), a multi-kinase inhibitor (tezevatinib), somatostatin analogues (lankreotide, octreotide), statins (pravastatin), mTOR inhibitors (everolimus, sirolimus), metformin in patients with autosomal recessive and autosomal polycystic kidney disease. The authors discuss the factors determining the prognosis and outcome of these diseases.
The pathogenesis and treatment of autosomal dominant polycystic kidney disease
AbstractAutosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disease which can occur at any age without obvious racial or gender preferences. Generally, the PKD1 and PKD2 genes are considered as the pathogenic genes for ADPKD. However, there are still some ADPKD patients in whom no pathogenic gene is detected. The PKD1 and PKD2 genes encode polycystic protein 1 (polycystin 1, PC1) and polycystic protein 2 (polycystin 2, PC2), respectively. PC1 and PC2 combine to form PC1/PC2 complex that is involved in regulating several common cell signaling pathways. At present, the treatment of ADPKD is mainly to delay the occurrence and progression of this disease. In the clinical, surgical treatment are common method and are effective. We present a review emphasizing the pathogenesis and current treatment of this condition.
Key words:
Autosomal dominant polycystic kidney disease; Pathogenic gene; Pathogenesis; Drug therapy
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.
