DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for polycystic kidney disease 2 — screening already-approved drugs against its 2-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 2 maps to a 2-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 polycystic kidney disease 2 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
polycystin 1, transient receptor potential channel interacting (PKD1) — PKD1 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 1rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ZKH · 2.3 Å · ligand (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl
(9Z)-octadec-9-enoate (PGW). Experimental structure, not a prediction.
What the evidence adds up to
Autosomal dominant polycystic kidney disease (ADPKD) accounts for 5–8% of the entire end-stage renal disease population. In 80–85% of cases the gene involved is PKD1; in the remaining 10–15% the disease is caused by mutations in PKD2, which encodes polycystin-2, a transmembrane protein that acts as a nonspecific calcium-permeable channel. Both polycystins function together in a common pathway; loss of function due to a germ-line mutation followed by a second somatic mutation in tubular cells results in loss of the normal terminally differentiated state, reversion to a less differentiated phenotype, and proliferation that leads to cyst formation. The primary cilia of tubular cells act as mechanoreceptors, and both polycystins are located within the cilia as mediators of mechanosensation.
No therapies have yet been discovered that prevent or inhibit cystogenesis. A 2019 review reports the results of clinical trials of vasopressin V2 receptor antagonists (tolvaptan, liksivaptan), a multi-kinase inhibitor (tezevatinib), somatostatin analogues (lanreotide, octreotide), statins (pravastatin), mTOR inhibitors (everolimus, sirolimus), and metformin in patients with autosomal recessive and autosomal dominant polycystic kidney disease. Another 2019 review states that current treatment is mainly to delay the occurrence and progression of the disease, and that surgical treatment is common and effective. A 2016 report notes that the main treatment is adequate renoprotective therapy, haemodialysis, and organ transplantation.
The abstracts do not provide concrete numbers for survival, response rates, or sample sizes for any of the drugs mentioned. No single drug is shown to be effective in a controlled trial with quantitative outcomes. What is still missing is evidence from adequately powered, randomised trials that report hard endpoints such as time to renal failure or death, and a clear understanding of which patient subgroups (for example, those with PKD2 versus PKD1 mutations) might benefit from a given intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Advances in Anatomic Pathology · 2005 · 40 citations
Molecular Basis of Autosomal Dominant Polycystic Kidney Disease
AbstractAutosomal dominant polycystic kidney disease (ADPKD) is a serious, life-threatening genetic disease in which extensive epithelial-lined cysts develop in the kidneys and, to a lesser extent, in other organs such as liver, pancreas, and ovaries. In a majority of cases (80-85%), the gene involved is PKD1, which is located on chromosome 16 (16q13.3) and encodes polycystin-1, a large receptor-like integral membrane protein that contains several extracellular motifs indicative of cell-cell and cell-matrix interaction. In the remaining (10-15%) cases, the disease is milder and is caused by mutational changes in another gene (PKD2), which is located at chromosome 4 (4q21-23) and encodes polcystin-2, a transmembrane protein, which acts as a nonspecific calcium-permeable channel. Both polycystins function together in a nonredundant fashion, through a common pathway, and produce cellular responses that regulate proliferation, migration, differentiation, and kidney morphogenesis. Through combined function of polycystins, normal tubular cells are maintained in a state of terminal differentiation, and their proliferation is strictly controlled. Loss of function of either protein due to gene mutations results in the tubular cells reverting to a less differentiated state, which is more prone to proliferation. Patients with ADPKD carry a germ-line mutation in PKD1 or PKD2. A second somatic mutation in some of the tubular cells results in loss of both normal alleles, leading to loss of polycystin function. The affected cells lose the normal terminally differentiated state, revert to less differentiated phenotype, and undergo proliferation, which leads to cyst formation. As the cysts enlarge over many decades, the normal renal parenchyma is progressively destroyed, leading to renal failure. Recently, the crucial role of primary cilia in modulating proliferation, migration, and differentiation of tubular epithelium has been recognized. Most of the tubular cells have one or two primary cilia projecting from the apical surface into the luminal space. The cilia act as mechanoreceptors as they bend with the urinary flow within the tubules. Both polycystins are strategically located within the cilia and act as important mediators of ciliary mechanosensation. Loss of this important function due to mutational changes in PKD1 or PKD2 leads to loss of normal control over cellular proliferation, resulting in cyst formation. Several other ciliary proteins have recently been found to contribute directly to a wide spectrum of human kidney diseases with cystic phenotype, thus underscoring the pivotal role the primary cilia play in maintaining the normal structure and function of the tubular cells and probably other cells in the body.
AbstractRenal cysts are common clinical findings, often incidentally discovered in the course of evaluating other problems. They may be either acquired or seen in association with a number of inherited and congenital disorders. The most common disorder, autosomal dominant polycystic kidney disease (ADPKD), is an important cause of end-stage renal disease (ESRD), accounting for 5–8% of the entire ESRD population. At the time of Dalgaard' s sentinel description of polycystic kidney disease (PKD), death from renal failure was a frequent outcome for affected individuals. While transplantation and dialysis have improved the prognosis for those suffering from PKD, no therapies have yet been discovered that prevent or inhibit cystogenesis. Hindering their development has been an incomplete knowledge of the pathogenesis of this process. Although most types of renal cysts share some common features (cell proliferation, basement membrane abnormalities, fluid secretion), the broad range of disorders associated with renal cysts suggests that defects in multiple, possibly intersecting, pathways are responsible for cyst formation and expansion. Recent molecular genetic studies have yielded important breakthroughs that are likely to lead to the unraveling of this mystery. In this chapter, we will review these data and how they have improved our understanding of renal cystic 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
Progress in molecular genetics 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.
Likarska sprava · 2016 · 0 citations · open access
The particulares of the hereditory renal polycystosis with children (information from science literature and own observation)
AbstractThe article deals with features of polycystic kidney disease according to literature data and results of own clinical observations. Diagnostics of the disease is difficult and includes genetic consultation and complex examination of main clinical and instrumental indexes. The main in treatment is adequate renoprotective therapy, hemodialysis with further organ transplantation.
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.
