DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for polycystic kidney disease 4 — 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 4 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 4 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
SHOC2 leucine rich repeat scaffold protein (SHOC2) — SHOC2 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7UPI · 2.89 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
Polycystic kidney disease 4 is one of a group of inherited disorders that result in tubular dilatation and the development of fluid-filled cysts in the kidney. The defective proteins in these diseases localise to the primary cilia and basal body, and the pleiotropic phenotypes are often associated with defective ciliogenesis. Data indicate that the polycystins are involved in ciliary mechanosensation and cellular changes in intracellular calcium and cAMP. Downstream cellular changes can be targeted, and potential therapeutic agents have proved highly effective in pre-clinical trials and are now being tested in patients. No therapies have yet been discovered that prevent or inhibit cystogenesis.
Autosomal dominant polycystic kidney disease accounts for 5–8% of the entire end-stage renal disease population. At the time of Dalgaard's sentinel description, death from renal failure was a frequent outcome for affected individuals. While transplantation and dialysis have improved the prognosis, hindering the development of therapies has been an incomplete knowledge of the pathogenesis. Most types of renal cysts share some common features: cell proliferation, basement membrane abnormalities, and 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.
Important progress has 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. The primary defects in these disorders cannot be corrected at present.
What is still missing is a completed understanding of the intersecting pathways that cause cyst formation and expansion, and the results of the ongoing patient trials of agents that target downstream cellular changes. No trial design or patient stratification strategy has yet been shown to yield a therapy that prevents or inhibits cystogenesis in humans.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Nephrology & Hypertension · 2006 · 42 citations
Understanding pathogenic mechanisms in polycystic kidney disease provides clues for therapy
AbstractPURPOSE OF REVIEW: Polycystic kidney diseases are a group of inherited disorders that result in tubular dilatation and/or the development of fluid-filled cysts in the kidney. Identification and analysis of the primary defective protein in many of these diseases are providing insights into a common pathogenesis to polycystic kidney disease. This review explores this pathogenesis and determines the role that this knowledge is playing in the development of potential therapies. RECENT FINDINGS: Study of simple and syndromic forms of polycystic kidney disease has revealed that the defective proteins are localized to the primary cilia/basal body and that the pleiotropic phenotypes are often associated with defective ciliogenesis. Data indicating that the polycystins are involved in ciliary mechanosensation, and cellular changes in intracellular Ca and cAMP, have provided clues for possible therapeutic approaches that have proved highly effective in pre-clinical trials. SUMMARY: Polycystic kidney diseases are associated with defects to proteins involved in developing functional, sensory cilia in the kidney. While the primary defects in these disorders cannot be corrected at present, downsteam cellular changes can be targeted. Potential therapeutic agents are now being tested in patients, moving polycystic kidney disease research into a new and exciting phase.
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.
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.
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.
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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