DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for calcium metabolic disease — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCalcium metabolic disease maps to a 5-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
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedPamidronateFarnesyl diphosphate synthase inhibitorapprovedAlendronateApproved drugapprovedCinacalcetApproved drug
Structures already discussed alongside calcium metabolic disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Structure of a three-domain sesquiterpene synthase: a prospective target for advanced biofuels production — Pamidronate has a real, experimentally solved structure in complex with this target (PDB 3SDR, 1.86 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 210drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3SDR · 1.86 Å · ligand Pamidronate (210). Experimental structure, not a prediction.
What the evidence adds up to
A 2009 randomised, placebo-controlled trial of 340 overweight and obese adults (mean age 38.8 years) found that 1500 mg/day of elemental calcium as calcium carbonate for two years produced no statistically or clinically significant difference in body weight change compared with placebo (difference 0.02 kg, 95% CI -1.64 to 1.69 kg; P = 0.98). Body fat mass also did not differ (difference 0.39 kg, 95% CI -1.04 to 1.92 kg; P = 0.55). Parathyroid hormone concentrations did decrease in the calcium group. The authors concluded that calcium supplementation is unlikely to have clinically significant efficacy as a preventive measure against weight gain in such patients.
A 2020 review of the relationship between calcium and obesity notes that the anti-obesity effect of calcium has been demonstrated by animal studies, observational population studies and randomised clinical studies, but also states that some studies have failed to explain the effect of calcium in obesity treatment. The review calls for larger studies, acknowledging that the protective effects are promising but not established.
A 2013 review of calcium renal lithiasis describes it as a frequent condition with high recurrence, associated with metabolic changes such as hypercalciuria and hypocitraturia, and with disorders including obesity. It states that once a metabolic diagnosis is made, dietary and pharmacological treatment can be established. Advances mentioned include the use of sodium alendronate in patients with calcium renal lithiasis and osteopenia or osteoporosis, and the combination of a thiazide with a bisphosphonate. The review notes that calcium renal lithiasis often requires multidrug treatment with strict follow-up.
A 2020 retrospective analysis of 2094 patients with nasopharyngeal carcinoma found that low serum calcium levels before antitumour therapy were detected in 53% of patients and were associated with poorer overall survival (P = 0.011), disease-free survival (P = 0.012) and distant metastasis-free survival (P = 0.004), but not with relapse-free survival (P = 0.376). Low serum calcium was an independent prognostic factor for those three outcomes. This study does not test calcium supplementation; it reports an association between a pre-treatment blood test result and survival in one cancer type.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Internal Medicine · 2009 · 92 citations · open access
Effects of Calcium Supplementation on Body Weight and Adiposity in Overweight and Obese Adults
AbstractBACKGROUND: Some data suggest that increasing calcium intake may help prevent weight gain. OBJECTIVE: To test the hypothesis that calcium supplementation can prevent weight gain in persons who are overweight or obese. DESIGN: Randomized, placebo-controlled trial. Randomization was computer-generated, and allocation was assigned by pharmacy personnel who prepared intervention and placebo capsules. Participants, providers, and those who assessed outcomes were blinded to study group assignment. SETTING: Single research center. PARTICIPANTS: 340 overweight (body mass index [BMI], 25 to <30 kg/m(2)) and obese (BMI > or =30 kg/m(2)) adults (mean age, 38.8 years [SD, 10.5]). INTERVENTION: Calcium carbonate (elemental calcium, 1500 mg/d) (n = 170) or placebo (n = 170) with meals for 2 years. MEASUREMENTS: Changes in body weight and fat mass (primary outcomes). RESULTS: Seventy-five percent of participants completed the trial (78% received calcium; 73% received placebo). There were no statistically or clinically significant differences between the calcium and placebo groups in change in body weight (difference, 0.02 kg [95% CI, -1.64 to 1.69 kg]; P = 0.98), BMI (difference, 0.32 kg/m(2) [CI, -0.41 to 1.02 kg/m(2)]; P = 0.39), or body fat mass (difference, 0.39 kg [CI, -1.04 to 1.92 kg]; P = 0.55). Parathyroid hormone concentrations decreased in the calcium group compared with the placebo group (difference, -0.71 pmol/L [CI, -1.28 to -0.13 pmol/L]). LIMITATION: The study took place at a research center, and its sample was mostly women. CONCLUSION: Dietary supplementation with elemental calcium, 1500 mg/d, for 2 years had no statistically or clinically significant effects on weight in overweight and obese adults. Calcium supplementation is unlikely to have clinically significant efficacy as a preventive measure against weight gain in such patients.
Pharmacoepidemiology and Drug Safety · 2015 · 14 citations
Management of serum calcium reductions among patients on hemodialysis following cinacalcet initiation
AbstractPURPOSE: Cinacalcet is indicated for treatment of secondary hyperparathyroidism in patients receiving hemodialysis. Cinacalcet reduces serum calcium concentrations by decreasing parathyroid hormone secretion, but the frequency and degree of calcium reduction following cinacalcet initiation, subsequent physician response, and ultimate calcium recovery in clinical practice are not well described. METHODS: Patients receiving hemodialysis at a large dialysis organization who enrolled in the organization's prescription benefits service and initiated cinacalcet at serum calcium ≥8.4 mg/dL were studied (N = 13 723). Patients were categorized by whether they experienced a reduction in calcium to <8.4 mg/dL and to what level (<7.5, 7.5-7.9, and 8.0-8.3 mg/dL). Baseline characteristics, frequency of subsequent intervention, and calcium recovery were compared. RESULTS: Of those who experienced a reduction in calcium to <8.4 mg/dL (n = 6437 [46.9%]), 6.6% had calcium <7.5 mg/dL and 24.5% had calcium 7.5-7.9 mg/dL, while the majority (68.9%) had a level of 8-8.3 mg/dL. Higher baseline parathyroid hormone and alkaline phosphatase were associated with lower resultant calcium. Among patients with calcium reductions, 45.6-63.5% received one or more directed clinical therapeutic responses, including 15.6-28.4% for whom cinacalcet was discontinued; the majority of patients recovered to calcium ≥8.4 mg/dL within 90 days of first detection. Only modest differences in recovery were noted between patients who did and did not receive any therapeutic response and patients who did and did not discontinue cinacalcet. CONCLUSION: Serum calcium reductions following cinacalcet initiation were common; declines <7.5 mg/dL were infrequent. Calcium recovery occurred in the majority of patients, with or without therapeutic intervention.
Sao Paulo Medical Journal · 2013 · 9 citations · open access
Calcium renal lithiasis: metabolic diagnosis and medical treatment
AbstractCalcium renal lithiasis is a frequent condition that affects the worldwide population and has a high recurrence rate. Different metabolic changes may trigger the onset of calcium stone disorders, such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and others. There are also other very prevalent disorders that are associated with calcium calculi, such as arterial hypertension, obesity and loss of bone mineral density. A correct diagnosis needs to be obtained through examining the serum and urinary parameters of mineral metabolism in order to carry out adequate prevention and treatment of this condition. Once the metabolic diagnosis is known, it is possible to establish dietary and pharmacological treatment that may enable monitoring of the disease and prevent recurrence of stone formation. Some advances in treating this pathological condition have been made, and these include use of sodium alendronate in patients with calcium renal lithiasis and osteopenia/osteoporosis, or use of a combination of a thiazide with a bisphosphonate. In summary, calcium renal lithiasis often requires multidrug treatment with strict control and follow-up of patients.
OncoTargets and Therapy · 2020 · 8 citations · open access
Serum Calcium Levels Before Antitumour Therapy Predict Clinical Outcomes in Patients with Nasopharyngeal Carcinoma
AbstractPurpose: The prognostic value of serum calcium levels in nasopharyngeal carcinoma (NPC) remains unknown. This study aimed to evaluate the prognostic value of serum calcium levels in patients with NPC. Patients and Methods: A total of 2094 patients diagnosed with NPC between April 2009 and September 2012 were enrolled in this retrospective analysis. The median follow-up time was 96.3 months (range: 4.1– 120.0 months). Univariate and multivariable Cox proportional hazards models were used to identify significant and independent prognostic predictors of overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS). Results: Overall, low serum calcium levels were detected in 1109/2094 (53.00%) patients and tended to be more frequently detected in older ( P < 0.001) and female ( P =0.001) patients. Patients with low serum calcium levels had poorer OS ( P =0.011), DFS ( P =0.012) and DMFS ( P =0.004) than those with high serum calcium levels, but serum calcium levels had no significant effect on RFS ( P =0.376). In univariate and multivariable analyses, low serum calcium levels were a statistically significant and independent prognostic factor for OS, DFS, and DMFS but had no prognostic value for RFS. Conclusion: Serum calcium levels can serve as a prognostic predictor and guide more individualized treatment for NPC patients. Keywords: nasopharyngeal carcinoma, serum calcium level, prognosis, survival
Demiroglu Science University Florence Nightingale Journal of Medicine · 2020 · 3 citations · open access
The relationship between calcium and obesity
AbstractDietary and behavioral approaches to obesity, a serious public health problem worldwide, have not prevented the progression of obesity. Scientists have explored the mechanisms of adipose tissue and intracellular calcium to find different therapeutic methods for obesity. Although the first step in the treatment of obesity is energy restriction, studies have shown that dietary calcium can play an important role not only in the regulation of skeletal integrity but also in energy metabolism. The anti-obesity effect of calcium has been demonstrated by animal studies, observational population studies and randomized clinical studies. However, some studies have failed to explain the effect of calcium in obesity treatment. Although the protective effects of calcium against obesity and comorbidities are promising, larger studies are needed. This review investigates the anti-obesity mechanisms of action of dietary calcium in animal studies, observational population studies, and randomized clinical trials.
AbstractThis report summarizes results of the clinical development program evaluating zoledronic acid (Zometa; Novartis Pharmaceuticals Corp, East Hanover, NJ) in the treatment of hypercalcemia of malignancy (HCM). In addition to a phase I dose escalation trial, two randomized, double-blind, double-dummy studies were conducted in parallel to investigate the clinical efficacy and safety of 4 mg and 8 mg zoledronic acid in patients with moderate to severe HCM. Patients were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or a control treatment, 90 mg pamidronate via 2-hour infusion. Patients who relapsed or had refractory HCM after initial treatment could be re-treated with 8 mg zoledronic acid. End points included rate of complete response, defined as normalization of corrected serum calcium by day 10, change in corrected serum calcium, time to relapse, duration of response, and bone biochemical markers. Doses of > or =0.02 mg/kg were effective and nontoxic in the phase I study. In the controlled studies, 287 patients were randomized and evaluated for safety and 275 patients were evaluable for efficacy. The proportions of patients with a complete response by day 10 were 88.4% and 86.7% in the 4 mg and 8 mg zoledronic acid groups, respectively, compared with 69.7% in the 90 mg pamidronate group. Corrected serum calcium normalization occurred by day 4 in 45.3% of patients treated with 4 mg zoledronic acid, 55.6% of patients treated with 8 mg zoledronic acid, and 33.3% of patients treated with pamidronate. Mean change from baseline in corrected serum calcium also was greater with zoledronic acid than with pamidronate. Median times to relapse were significantly longer in both the zoledronic acid 4 mg and 8 mg groups compared with the pamidronate group. There were no significant differences in efficacy between the 4 mg and 8 mg zoledronic acid doses. Retreatment in 69 patients with relapsing or refractory hypercalcemia with 8 mg zoledronic acid resulted in a 52% complete response rate. Fever, hypophosphatemia, and asymptomatic hypocalcemia were the most common drug-related adverse events. These studies have shown that a short single intravenous dose of 4 mg or 8 mg zoledronic acid is effective in treating moderate to severe HCM. Zoledronic acid produced a higher rate of calcium normalization, faster onset of action, and longer time to relapse than pamidronate, while maintaining an excellent safety profile. The lower dose of 4 mg is recommended as initial therapy, with the 8 mg dose reserved for patients requiring retreatment.
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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