DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperphosphatemia — 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 moduleHyperphosphatemia 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 hyperphosphatemia 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
solute carrier family 9 member A3 (SLC9A3) — SLC9A3 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~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7X2U · 3.2 Å · ligand [(2~{R})-2-hexadecanoyloxy-3-[oxidanyl-[(2~{S},3~{S},5~{R},6~{S})-2,3,4,5,6-pentakis(oxidanyl)cyclohexyl]oxy-phosphoryl]oxy-propyl] hexadecanoate (85R). Experimental structure, not a prediction.
What the evidence adds up to
In a cross-sectional analysis of 2,390 patients presenting at an emergency room in Switzerland, 215 had hyperphosphataemia and 10.7% of them died within 28 days, compared with 3.5% of the 480 hypophosphataemic patients. After adjusting for age, diuretic therapy and kidney function, hyperphosphataemia remained a strong independent risk factor for mortality (odds ratio 3.29, p<0.001). Hypophosphataemia showed no independent association with mortality. The study did not test any intervention.
Hyperphosphataemia in chronic kidney disease is managed with dialysis, dietary phosphorus restriction, phosphate-binding medications, and vitamin D analogs. Commercially available phosphate binders include calcium carbonate, calcium acetate, sevelamer, lanthanum, and rarely aluminium hydroxide. Aluminium-based binders are limited by known toxicities. Calcium carbonate works only over a narrow gastric pH range; calcium acetate is effective over a wider range. The use of sevelamer hydrochloride and lanthanum carbonate remains controversial. A 2007 review noted that new agents and therapeutic approaches for hyperphosphataemia in chronic kidney disease were under development but not yet licensed or available in routine practice.
In a study of 41 stable haemodialysis patients, the mean calcium–phosphate product was 50.5 mg²/dL² and the mean serum C-reactive protein was 8.6 mg/L. A significant positive correlation was found between log-transformed CRP and the calcium–phosphate product, and a significant inverse association between the product and patient age was observed. The authors concluded that the results point to a need for further attention to hyperphosphataemia in haemodialysis patients.
What remains missing are adequately powered randomised trials testing whether lowering serum phosphate with any specific binder or combination reduces mortality or cardiovascular events in dialysis or non-dialysis patients. The observational data cannot distinguish association from causation. No trial has yet stratified patients by baseline phosphate, inflammatory status, or residual kidney function to identify who might benefit. Funding for such trials, rather than for additional reviews or small correlational studies, is what is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2015 · 70 citations · open access
Hyperphosphatemia Is an Independent Risk Factor for Mortality in Critically Ill Patients: Results from a Cross-Sectional Study
AbstractBACKGROUND: Phosphate imbalances or disorders have a high risk of morbidity and mortality in patients with chronic kidney disease. It is unknown if this finding extends to mortality in patients presenting at an emergency room with or without normal kidney function. METHODS AND PATIENTS: This cross sectional analysis included all emergency room patients between 2010 and 2011 at the Inselspital Bern, Switzerland. A multivariable cox regression model was applied to assess the association between phosphate levels and in-hospital mortality up to 28 days. RESULTS: 22,239 subjects were screened for the study. Plasma phosphate concentrations were measured in 2,390 patients on hospital admission and were included in the analysis. 3.5% of the 480 patients with hypophosphatemia and 10.7% of the 215 patients with hyperphosphatemia died. In univariate analysis, phosphate levels were associated with mortality, age, diuretic therapy and kidney function (all p<0.001). In a multivariate Cox regression model, hyperphosphatemia (OR 3.29, p<0.001) was a strong independent risk factor for mortality. Hypophosphatemia was not associated with mortality (p>0.05). CONCLUSION: Hyperphosphatemia is associated with 28-day in-hospital mortality in an unselected cohort of patients presenting in an emergency room.
American Journal of Health-System Pharmacy · 2005 · 41 citations
Hyperphosphatemia and phosphate binders
AbstractPURPOSE: The pathophysiology of hyperphosphatemia associated with end-stage renal disease and treatment with phosphate binders are discussed. SUMMARY: Phosphorus is an essential element necessary for the normal function of the human body, required for skeletal construction and synthesis of DNA, proteins, and adenosine triphosphate. In healthy individuals, serum phosphorus concentrations are maintained between 2.5 and 4.5 mg/dL through diet and renal excretion. In renal insufficiency, phosphorus excretion declines and hyperphosphatemia develops. The body's compensation mechanisms cause secondary hyperparathyroidism and renal osteodystrophy. Phosphate binders provide an effective means for managing serum phosphate. Commercially available phosphate binders include calcium carbonate, calcium acetate, sevelamer, lanthanum, and, rarely, aluminum hydroxide. Because of aluminum's known toxicities, aluminum-based phosphate binders have a limited place in therapy. Calcium carbonate's benefits are seen over a narrow gastric pH range, thereby limiting the drug's utility. Calcium acetate is effective over a wide pH range. Other phosphate binders, including sevelamer hydrochloride and lanthanum carbonate, have recently entered the market, but their use remains controversial. CONCLUSION: If left untreated, hyperphosphatemia can result in secondary hyperparathyroidism, renal osteodystrophy, and metastatic calcification of blood vessels and soft tissue. The treatment of hyperphosphatemia in patients with chronic renal failure includes dialysis, dietary phosphorus restrictions, phosphate-binding medications, and vitamin D analogs. Selection of phosphate binders should be based on patient characteristics, including serum phosphate, serum calcium, and intact parathyroid hormone concentrations, and patient tolerability.
PHOSPHORUS METABOLISM AND MANAGEMENT IN CHRONIC KIDNEY DISEASE: New Developments in the Management of Hyperphosphatemia in Chronic Kidney Disease
AbstractHyperphosphatemia is a characteristic complication of significant chronic kidney disease. Elevated serum phosphorous is associated with reduced survival. Hyperphosphatemia has long been recognized as predisposing to uremic bone disease and disorders of parathyroid function. Furthermore, elevated serum phosphate has been implicated particularly in the development of cardiovascular structural and functional abnormalities. Given the limitations of restricting phosphate in the diet and the inadequate removal by conventional dialysis regimes, nephrologists rely on the use of additional medications to control serum levels (currently oral phosphate binders). This review focuses on new agents and therapeutic approaches dealing with hyperphosphatemia in chronic kidney disease, that are not currently licensed and available in routine clinical practise. This article attempts to review therapies under development and considers additional effects that the next generation of agents may bring over and above those already within the therapeutic armamentarium.
Hyperphosphatemia: Understanding the role of phosphate metabolism
AbstractLEARNING OBJECTIVES Describe the general characteristics of phosphate and its metabolism Discuss the causes of hyperphosphatemia Explain the manifestations and complications associated with hyperphosphatemia Review the diagnostic evaluation and treatment of elevated phosphate An elevated phosphate level is an indicator of serious disease. Identification of the underlying cause is based on which other diagnostic test results are abnormal. EARN CATEGORY I CME CREDIT by reading this article and the article beginning on page 20 and successfully completing the posttest on page 38. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of July 2010.
Association of Ca×PO4 product with levels of serum C-reactive protein in regular hemodialysis patients.
AbstractINTRODUCTION: Numerous studies have attempted to identify risk factors for mortality and morbidity in maintenance hemodialysis patients. In this study we sought to examine the association of the levels of serum C-reactive protein (CRP) with value of Ca×PO4 product, in stable hemodialysis patients. PATIENTS AND METHODS: Based on the severity of secondary hyperparathyroidism, patients being treated with oral active vitamin D3, calcium carbonate/Renagel tablets at various doses. Fasting serum 25-hydroxy vitamin D and intact serum parathormone and also serum blood urea nitrogen, CRP, calcium, phosphorus, alkaline phosphatase was measured. RESULTS: A total of 41 patients, enrolled to the study. The mean patients' age were 46(17.6) years. The value of serum CRP of patients was 8.6 (6.6) mg/l (median 6 mg/l). The value of Ca×PO4 product was 50.5(15.5) mg2/dl2 (median: 50 mg(2)/dl(2)). In this study, a significant inverse association between Ca×PO4 product and the age of the patients was seen. A significant positive correlation of logarithm of serum CRP with Ca×PO4 product was found. CONCLUSION: The result of this study, revealed the need to further attention to hyperphosphatemia in hemodialysis patients.
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.
