DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for phosphorus metabolism disease — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePhosphorus metabolism disease maps to a 12-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 phosphorus metabolism disease 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
HD domain containing 2 (HDDC2) — HDDC2 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-[2-(2-ethoxy-ethoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4L1J · 1.824 Å · ligand 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL (PE4). Experimental structure, not a prediction.
What the evidence adds up to
Acute phosphorus intoxication from ingestion of elemental yellow phosphorus carries a high mortality: one study recorded a 50% mortality rate, another 48% among those who ingested large doses. Two case reports describe patients who survived after ingesting approximately 715 mg and 350 mg of elemental phosphorus respectively; both had liver biopsies during the acute phase and again after apparent clinical recovery. Liver injury is common, but most victims die before overt liver lesions develop.
In patients on chronic haemodialysis with hyperphosphataemia, a retrospective analysis of pharmacy data for 1,029 adults prescribed sucroferric oxyhydroxide found that the proportion achieving serum phosphorus ≤ 5.5 mg/dL rose from 13.9% at baseline to 26.1% at 3 months and to 30.4% at 6 months (n=424). The mean prescribed phosphate binder pills per day fell from 9.6 to 3.8 at 3 months and from 9.7 to 4.0 at 6 months. These are observational data, not from a randomised trial.
A systematic review of calcium and phosphorus metabolism disorders in chronic kidney disease stages III–IV describes the physiological cascade: as glomerular filtration rate falls below 60 ml/min/1.73 m², phosphorus filtration decreases, parathyroid hormone secretion rises, and when GFR falls below 30 ml/min/1.73 m² persistent hyperphosphataemia develops. This is accompanied by calcitriol deficiency, hypocalcaemia, parathyroid gland hyperplasia, and secondary hyperparathyroidism. The review notes that cardiovascular disease is the leading cause of death in CKD patients and that there is a desperate need for randomised trials to guide treatment decisions.
Phosphorus deficiency in animals causes hypophosphataemia and bone diseases such as rickets and osteoporosis. In protozoa (Tetrahymena thermophile and Tetrahymena pyriformis), phosphate-poor medium leads to decreased cell growth, abnormal morphology, altered mobility, and reduced activity of both soluble and membrane inorganic pyrophosphatases. The authors suggest Tetrahymena could serve as a model for cellular phosphate stress. What remains missing are adequately powered randomised controlled trials in humans with phosphorus metabolism disorders, particularly for phosphate binders and for treatments addressing the underlying physiological disruptions at earlier stages of chronic kidney disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis
AbstractBACKGROUND: Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported. METHODS: In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed. RESULTS: A total of 253 patients were screened, 143 of whom were randomized (sevelamer hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well balanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001). CONCLUSIONS: In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients. The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis populations.
Archives of Internal Medicine · 1963 · 40 citations
Phosphorus Poisoning in Humans
AbstractAcute phosphorus intoxication has been a familiar syndrome for many years. It has been stated that ingestion of as little as 15 mg of elemental yellow phosphorus may cause symptoms, and 60 mg can be fatal. 2 In one study mortality rate was recorded as 50% 3 and, in another study, 48% of those who ingested large doses. 2 Elemental yellow phosphorus, but not red phosphorus, interferes with various physiological functions. Liver injury is common; however, most victims of phosphorus intoxication die before overt liver lesions develop. 2 The purpose of this paper is to report two cases in which patients survived the ingestion of large amounts of phosphorus. One patient ingested about 715 mg and the other about 350 mg of elemental phosphorus. Both of these patients had liver biopsies during the acute phase, and the biopsies were repeated after apparently complete clinical recovery. Both were admitted and studied
Clinical Nephrology · 2017 · 38 citations · open access
Real-world effectiveness of sucroferric oxyhydroxide in patients on chronic hemodialysis: A retrospective analysis of pharmacy data
AbstractAIMS: Hyperphosphatemia has been associated with an increased risk of mortality in patients with end-stage renal disease. We sought to assess the real-world effectiveness of sucroferric oxyhydroxide (SO), an iron-based phosphate binder (PB), in control of serum phosphorus levels, and to determine the associated pill burden in hemodialysis patients. MATERIALS AND METHODS: Adult, in-center hemodialysis patients first prescribed SO through a renal pharmacy service as part of routine clinical care between April 1, 2014 and March 31, 2015 were included in the analysis. The proportion of patients with phosphorus levels ≤ 5.5 mg/dL and the mean prescribed PB pills/day were compared between baseline (3 months prior to SO) and SO follow-up at 3 (SO 1 - 3) and 6 months (SO 4 - 6). Mineral bone disease markers, hemoglobin, iron indices, and erythropoiesis-stimulating agents and intravenous iron use were assessed. RESULTS: At baseline, all patients (n = 1,029) were prescribed PB, and 13.9% had mean serum phosphorus ≤ 5.5 mg/dL. Comparing baseline to SO 1 - 3, the mean prescribed PB pills/day declined from 9.6 to 3.8 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 13.9 to 26.1% (+88%). Comparing baseline to SO 4 - 6 (n = 424), the mean prescribed PB pills/day declined from 9.7 to 4.0 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 15.6 to 30.4% (+95%). CONCLUSIONS: Prescription of SO was associated with an increase in the proportion of patients achieving serum phosphorus levels ≤ 5.5 mg/dL along with fewer prescribed PB pills/day. .
Phosphorus and Calcium Metabolism Disorders Associated with Chronic Kidney Disease Stage III-IV (Systematic Review and Meta-Analysis)
AbstractKidneys play an important role in maintenance of the calcium and phosphorus balance. Renal failure is associated with disorders of all phases of the phosphorus and calcium turnover. The decrease of glomerular filtration rate (GFR) under 60 ml/min/1.73 m 2 is associated with phosphorus filtration rate decrease with further elevation of its serum level that results in parathyroid hormone (PTH) secretion stimulation. PTH suppresses phosphorus reabsorption; therefore, it returns its serum level to normal. However, when the GFR falls below the 30 ml/min/1.73 m 2 level, this mechanism becomes ineffective and persistent hyperphosphatemia develops. The latter enhances the PTH secretion. Hyperphosphatemia is associated with inhibition of 1 -hydroxylase effect in proximal renal tubules and the decrease of serum 1,25(OH) 2 D 3 (calcitriol) level. Calcitriol deficiency results in calcium absorption disorders in small intestine; as a result, hypocalcemia develops. Persistent hypocalcemia results in parathyroid glands hyperplasia (PTGH) that is associated with excessive PTH production and secretion. PTH hyper-production and hyperphosphatemia are the manifestations of secondary hyper-parathyroidism (SHPT). Hypocalcemia, vitamin D deficiency and hyperphosphatemia are the main factors responsible for secondary hyperparathyroidism. Hypocalcemia, vitamin D deficiency and hyperphosphatemia develop at the initial stage or renal dysfunction -Chronic Kidney Disease (CKD) III (GFR 60-30 ml/min/1.73 m 2 ); they progress with the increasing severity of renal failure (GFR 29-15 ml/min/1.73 m 2 , CKD IV-V). Disorders of calcium and phosphorus balance associated with CKD result in bone diseases, generally called renal osteodystrophy. At the same time numerous cohort studies have broadened the focus of CKD-related mineral and bone disorders to include cardiovascular disease ( which is the leading cause of death in patients at all stages of CKD). All three of these processes (abnormal mineral metabolism, abnormal bone and extra skeletal calcification) are closely interrelated and together make a major contribution to the morbidity and mortality of patients with CKD. Since the publication of the 2003 K/DOQI guidelines for bone and mineral metabolism, there has been tremendous advancement in our understanding of mineral metabolism in CKD patients. Major modifications of K/DOQI bone guidelines are essential and should www.intechopen.com Chronic Kidney Disease and Renal Transplantation 96 reflect our improved understanding of calcium and phosphorus metabolism. At the same time there is a desperate need for randomized trials for better informed decision making and further optimization of care of CKD patients. The aim of the review is to provide a literature summary concerning the diagnosis and treatment of mineral metabolism disorders in CKD, which will serve an action plan for clinicians.
Advances in Bioscience and Biotechnology · 2017 · 1 citations · open access
Cell Stress by Phosphate of Two Protozoa &lt;i&gt;Tetrahymena thermophile&lt;/i&gt; and &lt;i&gt;Tetrahymena pyriformis&lt;/i&gt;
AbstractPhosphorus is one of the bioelements most needed as a compound cell by living organisms. Phosphorus is involved in several pathologies: in human with bone and kidney diseases, in mammals with metabolism disorder (glucose, insulin···), in microorganisms whose phosphorus is involved in cell growth. Phosphorus has various forms including pyrophosphate, a by-product of multiple pathways of biosynthesis. Enzymes that hydrolyze pyrophosphate are called inorganic pyrophosphatases (PPases). Two major types of inorganic pyrophosphatases are distinguished: the soluble pyrophosphatases (sPPases) and the membrane pyrophosphatases (mPPases or H+/Na+-PPases). They play a key role in the control of intracellular inorganic pyrophosphate level and produce an important ions gradient (H+ or Na+) to the cells. In this work, we primarily focused on the physiological study in a phosphate-poor medium of two models Tetrahymena thermophile and Tetrahymena pyriformis, following the mobility, the growth and the morphology of cells. Secondly, we evaluated the enzymatic activity of soluble and membrane pyrophosphatases in both species grown in the same complex medium. A decrease of cell growth is correlated with unusual morphologies and different mobility in the stress medium. The measurement of soluble and membrane inorganic pyrophosphatases activities also shows a decrease which illustrates the lack of phosphate found in the stress medium. Deficiency of phosphate is a limiting factor for protozoan growth. These results indicate that Tetrahymena can be used as a model of cellular stress and consists of a target to study inorganic pyrophosphatases for a better understanding of phosphate cycle in higher organisms.
International Journal of Trend in Scientific Research and Development · 2018 · 0 citations · open access
Phosphorus Deficiency Phosphorous Deficiency in Animals
AbstractPhosphorus deficiency is a condition, in which Phosphorus is insufficient or is not utilized properly. Phosphorus is a mineral that is vitally important to the normal metabolism of numerous compounds & (in solution) an acid that, with sulphur, must be neutralized by the base-forming ions of sodium, potassium, calcium, & magnesium. About 70% of retained Phosphorus combines with calcium in bone & tooth structure. Phosphorus is the principal element in the structure of the nucleus & cytoplasm of all tissue cells. It is also a universally distributed component of skeletal, nerve, & muscle tissues. A reduced concentration of phosphorus in the blood serum is a disorder known as hypophosphatemia. Phosphorus deficiency may cause bone diseases such as rickets in animals. An improper balance of phosphorus & calcium may cause osteoporosis. Dietary sources of Phosp include milk products, egg yolk, legumes, nuts, &whole grains. ETIOLOGY 1. Deficiency of phosphorous in the diet. a) Soil deficient in phosphorous. b) Hay, kadbi and straws are naturally deficient in phosphorous. c) Drought conditions reduce phosphorous content in the forage. 2. Impaired absorption of phosphorous. a) Excess calcium, aluminium or iron in diet. b) Vit. D deficiency. c) Improper phosphorous and calcium ratio.
American Journal of Clinical Pathology · 2024 · 0 citations · open access
Sevelamer Treatment for Hyperphosphatemia in a Saudi Arabian Chronic Renal Disease Patient
AbstractAbstract Introduction/Objective Introduction: Patients with advanced chronic kidney disease (CKD) often require phosphate binders to manage elevated serum phosphorus levels due to phosphorus-restricted diets being insufficient. This study aimed to assess the safety and efficacy of sevelamer in lowering serum phosphorus and improving the serum lipid profile in a hemodialysis patient. Methods/Case Report A prospective study was conducted on a 59-year-old hemodialysis man with CKD. Sevelamer was administered orally as 800 mg tablets, with the dosage adjusted based on washout serum phosphorus levels (WSPL). Blood samples were collected every two weeks before dialysis, and all samples were analyzed using standard clinical laboratory methods. Sevelamer treatment resulted in a significant reduction in serum phosphorus levels from 6.9 mmol/l to 4.3 mmol/l. No major adverse events were observed during the trial period, and there was no evidence of negative consequences associated with sevelamer therapy. Additionally, sevelamer treatment led to a decrease in hemoglobin levels to 10.5 g/dl and a substantial reduction in total cholesterol concentration from 5.22 mmol/l to 4.26 mmol/l. Results (if a Case Study enter NA) NA Conclusion Conclusion: Sevelamer, a non-absorbable aluminum and calcium-free phosphate binder, effectively lowered serum phosphorus levels in dialysis patients while improving lipid profiles. It was well tolerated with no instances of hypercalcemia and resulted in significant reductions in intact parathyroid hormone (PTH) and total and LDL cholesterol. Sevelamer may serve as a valuable therapeutic option for managing hyperphosphatemia in patients with CKD.
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.
