DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Hypercalcemia — screening already-approved drugs against its 20-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypercalcemia maps to a 20-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 hypercalcemia 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
calcitonin receptor (CALCR) — CALCR 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8F0K · 1.9 Å · ligand (2S)-2-{[(1R)-1-hydroxyhexadecyl]oxy}-3-{[(1R)-1-hydroxyoctadecyl]oxy}propyl 2-(trimethylammonio)ethyl phosphate (P42). Experimental structure, not a prediction.
What the evidence adds up to
In a 1989 retrospective analysis of 7667 patients registered at a comprehensive cancer centre, severe hypercalcemia (serum calcium above 12.0 mg/100 ml) occurred in 40 patients (0.52%) and moderate hypercalcemia (10.8–12.0 mg/100 ml) in 48 patients (0.63%). The highest rates of severe hypercalcemia were in renal cell cancer (1.42%) and non-small cell lung cancer (1.03%); moderate hypercalcemia was most frequent in renal cell cancer (3.30%) and multiple myeloma (2.38%). Hypercalcemia was associated with increased distant metastases, bone metastases, and higher mortality. The authors concluded that while hypercalcemia can appear as a frequent complication at some point, its incidence is relatively low.
A 1996 case report describes an infant with multisystem Langerhans cell histiocytosis who developed hypercalcemia on two occasions. After being placed on indomethacin, the hypercalcemia did not recur despite progression of the underlying disease. The authors concluded that indomethacin should be considered as a treatment for hypercalcemia in this setting.
A 1983 review of 72 admissions (53 patients) for hypercalcemia-related diseases lists hydration, forced diuresis, oral phosphates, and glucocorticosteroid drugs as common therapeutic approaches. The authors note that combination therapy with glucocorticosteroids, oral phosphates, and forced diuresis is used to exploit multiple mechanisms of action, and that most patients are treated when serum calcium reaches 12 mg/dL or above. An algorithm is presented but no comparative efficacy data from controlled trials are given.
Two cases of late-onset hypercalcemia associated with teriparatide (recombinant human parathyroid hormone 1-34) are reported from 2022. A 54-year-old man developed asymptomatic hypercalcemia of 11.2 mg/dL six months into treatment; his calcium normalised and treatment continued. A 75-year-old woman developed asymptomatic hypercalcemia of 12.5 mg/dL after six months; teriparatide was held and calcium normalised. The authors note that transient hypercalcemia usually resolves within 16 hours of dosing, that late hypercalcemia (beyond 24 hours) is rare, usually mild and asymptomatic, and that treatment disruption occurs in 0.18–4% of cases. No controlled trial data are provided. What remains missing is prospective, randomised evidence comparing any of these interventions against each other or against placebo, and stratification by tumour type or mechanism of hypercalcemia.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 1993 · 137 citations · open access
Incidence of hypercalcemia in patients with malignancy referred to a comprehensive cancer center
AbstractBACKGROUND: Hypercalcemia is a serious and not infrequent complication of malignant diseases; precise information about the incidence of hypercalcemia is not readily available. The study was designed to determine the incidence of hypercalcemia in patients with cancer. METHODS: Retrospective analysis was done of laboratory data from 7667 patients registered at M.D. Anderson Cancer Center for the first time during 1989 for whom serum calcium levels were determined during the first 2 months after registration. RESULTS: Severe hypercalcemia (serum calcium level of more than 12.0 mg/100 ml) was present in 40 patients (0.52%); it occurred most often in patients with renal cell cancer (1.42%) and non-small cell lung cancer (1.03%). Less frequent diagnoses were multiple myeloma (0.79%), leukemia (0.63%), non-Hodgkin lymphoma (0.26%), and cancer of the gastrointestinal tract (0.20%). Moderate hypercalcemia (calcium levels of 10.8-12.0 mg/100 ml) was present in 48 patients (0.63%); it occurred most often in patients with renal cell cancer (3.30%) and multiple myeloma (2.38%). Less frequent diagnoses were non-small cell lung cancer (0.89%), non-Hodgkin lymphoma (0.79%), leukemia (0.63%), and cancer of the gastrointestinal tract (0.51%). The presence of hypercalcemia was associated with increased frequency of distant metastases, bone metastases, and increased mortality consistent with other studies of the prognostic effect of this complication. CONCLUSIONS: Hypercalcemia may appear as a frequent complication in patients with cancer at some time during the course of their disease, but its incidence is relatively low.
Journal of Pediatric Hematology/Oncology · 1996 · 15 citations
Langerhans Cell Histiocytosis and Hypercalcemia
AbstractPURPOSE: Hypercalcemia is a known complication of childhood malignancies but has never been reported to be associated with Langerhans cell histiocytosis (LCH) in a pediatric patient. PATIENTS AND METHODS: We describe an infant with multisystem LCH who developed hypercalcemia on two occasions. After being placed on indomethacin, the hypercalcemia did not recur despite disease progression. CONCLUSION: Hypercalcemia may complicate LCH. If it is demonstrated, indomethacin should be considered as a treatment.
AbstractThe indications, effectiveness, and adverse effects of the numerous treatment modalities for hypercalcemia are presented. Results of a retrospective chart review of 72 admissions (53 patients) for hypercalcemia-related diseases are presented to emphasize the therapeutic principles that should be applied in the management of these patients. Hydration, forced diuresis, oral phosphates, and glucocorticosteroid drugs are common therapeutic approaches. Combination therapy with glucocorticosteroid drugs, oral phosphates, and forced diuresis is utilized to take advantage of multiple mechanisms of action. Outpatient therapy for hypercalcemia consists primarily of glucocorticosteroid agents and oral phosphates. Most patients are treated if the serum calcium level is greater than or equal to 12 mg/dL. An algorithm is presented to assist the clinician in selecting the most efficacious treatment plan.
Journal of Community Hospital Internal Medicine Perspectives · 2022 · 6 citations · open access
Teriparatide-Associated Late Hypercalcemia: A Report of Two Cases and Literature Review
AbstractIntroduction: Teriparatide, recombinant human parathyroid hormone (1-34), is a safe and usually well-tolerated medication. We describe two cases of late-onset hypercalcemia associated with teriparatide use and report current evidence of hypercalcemia during the treatment with PTH analogs. Case report: Case 1 is a 54-year-old man with a history of osteoporosis, previously treated with 6 months of teriparatide, but had not been consistent in taking the medication. Before restarting teriparatide, his serum calcium, PTH and vitamin D were normal. Six months into the treatment, he developed asymptomatic hypercalcemia of 11.2 mg/dL 24 h after the last dose. Repeat serum calcium was normal and treatment was continued. Case 2 is a 75-year old woman with a history of osteopenia and severe scoliosis. Before starting teriparatide, her calcium, PTH and vitamin D were normal. Six months into the treatment, she developed asymptomatic hypercalcemia of 12.5 mg/dL. Teriparatide was held and subsequently her serum calcium normalized. Discussion: Transient hypercalcemia can occur during treatment with teriparatide and usually resolves within 16 h after administration. Late hypercalcemia, occurring more than 24 h after the dose, is rarely seen. It is usually mild, asymptomatic and rarely occurs repeatedly. Hypercalcemia occurs more often in patients with pre-existing hypercalcemia or vitamin D deficiency. It is rarely a cause of treatment disruption (0.18-4%). Conclusion: Clinicians should be aware of this side effect, especially in patients who may be at risk of complications of hypercalcemia.
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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