DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for parathyroid disease — screening already-approved drugs against its 34-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleParathyroid disease maps to a 34-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
approvedDoxercalciferolVitamin D receptor agonistapprovedParicalcitolApproved drug
Structures already discussed alongside parathyroid disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of CYP2R1 — Doxercalciferol has a real, experimentally solved structure in complex with this target (PDB 3DL9, 2.721 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 v2hdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3DL9 · 2.721 Å · ligand Doxercalciferol (V2H). Experimental structure, not a prediction.
What the evidence adds up to
In eleven patients with Paget’s disease treated with salmon calcitonin for up to 23 months, basal plasma calcium, parathyroid hormone, and serum phosphorus remained in the normal range and did not change significantly. An acute fall in calcium and a rise in parathyroid hormone occurred after the initial injection, and the rise in parathyroid hormone remained proportional to the fall in calcium after treatment, indicating no secondary hyperparathyroidism developed. A 1939 case report describes postoperative parathyroid tetany controlled by dihydrotachysterol after other treatments had failed; the author notes tetany still occurs in about 1.5 per cent of cases after subtotal thyroidectomy and that parathyroid solution does not control every case.
In 35 chronic kidney disease stage 4 patients with secondary hyperparathyroidism, oral doxercalciferol reduced mean intact parathyroid hormone by 35.4 ± 4.4% from 381.7 ± 31.3 pg/mL to 237.9 ± 25.7 pg/mL over 18 weeks. 83% of patients achieved at least a 30% suppression and 72% achieved at least a 50% suppression. Mean serum calcium, phosphorus, and calcium-phosphorus product did not differ significantly from baseline, but four patients developed hypercalcemia, two developed severe hyperphosphatemia, and nine had a calcium-phosphorus product above 55. 21 patients required temporary stoppage of therapy, and most restarted at a reduced dose.
In 24 end-stage renal disease patients with secondary hyperparathyroidism, ultrasound-guided local paricalcitol injection reduced intact parathyroid hormone from 1887.81 ± 726.81 pg/mL to 631.06 ± 393.06 pg/mL after six months, with a decrease in parathyroid gland volume from 0.87 ± 0.50 cm³ to 0.60 ± 0.36 cm³ and relief of ostealgia within 48–72 hours. In 22 patients who received intravenous paricalcitol, intact parathyroid hormone fell from 686.87 ± 260.44 pg/mL to 388.47 ± 167.36 pg/mL, with no significant change in phosphate or gland volume. No severe complications occurred in either group, and in vitro analysis indicated paricalcitol induced parathyroid cell apoptosis in a dose-dependent manner.
In 44 Chinese maintenance hemodialysis patients with secondary hyperparathyroidism, intermittent intravenous doxercalciferol (initial dose 4 μg three times weekly for 12 weeks) reduced intact parathyroid hormone from a baseline of 655.05 pg/mL to 269.90 pg/mL, a mean percentage change of -55.45% ± 20.08%. 86.4% of patients achieved at least a 30% reduction. At week 12, 80% of patients in the mild group (baseline iPTH 400–599.99 pg/mL) had intact parathyroid hormone within or below the target range of 150–300 pg/mL, compared to 41.76% in the moderate group and 33.33% in the severe group. Hypercalcemia occurred in 33.3% of patients, with severe hypercalcemia in 8.9%, all resolved after dose reduction or discontinuation. What remains missing are randomised controlled trials comparing these vitamin D analogues head-to-head, long-term safety data beyond 18–24 weeks, and prospective studies that stratify patients by parathyroid gland volume or baseline hormone level to predict who benefits from local versus systemic therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Endocrinology · 1973 · 34 citations
PARATHYROID FUNCTION IN PATIENTS WITH PAGET'S DISEASE TREATED WITH SALMON CALCITONIN
AbstractSUMMARY To study the possibility of secondary hyperparathyroidism in patients with Paget's disease treated with calcitonin over a long period, we investigated parathyroid function in eleven patients treated with salmon calcitonin (CT) for up to 23 months and in one patient treated with human CT. Basal plasma calcium, immuno‐reactive parathyroid hormone (PTH) and serum phosphorus levels were all in the normal range before and after the treatment and did not change significantly during the treatment. In all patients, an acute fall in calcium and a rise in PTH occurred after the initial injection of CT. The rise in PTH was proportional to the fall in calcium and similar to that observed in normal subjects. After treatment, the rise in plasma PTH remained the same in relation to the fall in calcium, indicating that the responsiveness of the parathyroid glands to the hypocalcaemic challenge was unaltered, and that secondary hyperparathyroidism was not present in these patients.
AbstractThe case of postoperative parathyroid tetany that we are reporting here merits, we believe, the attention of the practitioner because of the dramatically efficacious control of the disease effected by means of dihydrotachysterol (A. T. 10), whereas every form of treatment attempted previously was without any beneficial result. There are, moreover, few reports in the American literature dealing with the clinical use of dihydrotachysterol in the treatment of postoperative parathyroid tetany. Despite all precautions and meticulous surgical technic, postoperative parathyroid tetany, following subtotal thyroidectomy, still occurs in about 1.5 per cent of cases. The prevailing impression that with the advent of solution of parathyroid an answer was found to the problem of controlling every case of parathyroid tetany has been shown, as in the case to be reported here, to be erroneous. Although parathyroid tetany may yield readily to treatment with adequate dosage of calcium and cod liver oil, cases
Indian Journal of Nephrology · 2013 · 3 citations · open access
Efficacy and safety of oral doxercalciferol in the management of secondary hyperparathyroidism in chronic kidney disease stage 4
AbstractThis study was carried out to evaluate the efficacy and safety of doxercalciferol as therapy for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 4 in a prospective clinical trial. A total of 35 CKD-4 patients who had a baseline parathyroid hormone (iPTH) >150 pg/mL and had not received any vitamin D analog in the preceding 8 weeks were followed up at intervals of 6 weeks for 18 weeks on oral therapy with doxercalciferol. The starting dose was 1.5 μg/day, and the dose was increased in steps of 1 μg/day if iPTH did not decrease by at least 30% on the subsequent visit. Doxercalciferol was stopped temporarily if low iPTH (<70 pg/mL), hypercalcemia (>10.7 mg/dL), or severe hyperphosphatemia (>8.0 mg/dL) occurred, and was restarted at a lower dose on reversal of these abnormalities. Calcium acetate was the only phosphate binder used. Mean iPTH decreased by 35.4 ± 4.4% from 381.7 ± 31.3 pg/mL to 237.9 ± 25.7 pg/mL (P < 0.001). The proportion of patients who achieved 30% and 50% suppression of iPTH levels was 83% and 72%, respectively. Mean serum calcium, phosphorus, and calcium-phosphorus product values did not differ significantly from the baseline values. Four, two, and nine patients developed hypercalcemia, severe hyperphosphatemia, and high CaxP (>55), respectively. Almost all patients recovered to an acceptable level within 2 weeks of stopping doxercalciferol and adjusting the phosphate binder dose. In all, 21 patients required temporary stoppage of therapy. Most of them were restarted on therapy at a reduced dose during the study. It can, therefore, be concluded that doxercalciferol is effective in controlling SHPT in CKD-4 patients with an acceptable risk of hyperphosphatemia and hypercalcemia.
Journal of Clinical Medicine · 2022 · 3 citations · open access
Effectiveness and Safety of Ultrasound-Guided Local Paricalcitol Injection in Treating Secondary Hyperparathyroidism in ESRD: A Retrospective Study
AbstractPurpose: To compare the safety and efficacy of percutaneous paricalcitol injection with intravenously administered paricalcitol in treating parathyroid hyperplasia in patients with secondary hyperparathyroidism (SHPT). Methods: This study was approved by the Ethics Committee of our institution. We retrospectively collected data on patients who received percutaneous paricalcitol injection (24 patients) and intravenously administered paricalcitol (22 patients) based on their intact parathyroid hormone (iPTH) level. Serum iPTH, calcium, phosphorus, and the volume of the parathyroid gland were measured at several indicated time points after treatment, and adverse events associated with the two treatments were evaluated. Results: After 6 months of follow-up, we found that patients from the percutaneous injection group had significantly decreased levels of iPTH (from 1887.81 ± 726.81 pg/mL to 631.06 ± 393.06 pg/mL), phosphate (from 1.94 ± 0.36 mmol/L to 1.71 ± 0.34 mmol/L), and volume of the parathyroid gland (from 0.87 ± 0.50 cm3 to 0.60 ± 0.36 cm3), with relief from ostealgia within 48–72 h. In the intravenously administered group, the levels of iPTH decreased from 686.87 ± 260.44 pg/mL to 388.47 ± 167.36 pg/mL; while there was no significant change in phosphate levels, the volume of the parathyroid gland and ostealgia relief were observed at the end of follow-up. The serum calcium level did not significantly change, and no severe complications were observed in both groups. In vitro fluorescence-activated single cell sorting (FACS) analysis indicated that paricalcitol induced parathyroid cell apoptosis in a dose-dependent manner. Conclusions: Percutaneous paricalcitol injection is a selective treatment for SHPT in ESRD.
Frontiers in Pharmacology · 2025 · 1 citations · open access
Efficacy and safety of intermittent intravenous doxercalciferol in the treatment of secondary hyperparathyroidism in Chinese patients on maintenance hemodialysis: a phase II, open-label, prospective, multicenter study
AbstractObjective: This phase II, open-label, prospective, multicenter study evaluated the efficacy and safety of intermittent intravenous doxercalciferol in treating secondary hyperparathyroidism (SHPT) in Chinese maintenance hemodialysis (MHD) patients. Methods: MHD patients aged 18 to 75 years with a serum intact parathyroid hormone (iPTH) level of 400 pg/mL or higher were enrolled and stratified into Mild, Moderate, and Severe groups based on baseline iPTH levels (400-599.99, 600-799.99, and ≥800 pg/mL, respectively). Patients received an initial dose of 4 μg of doxercalciferol three times weekly for 12 weeks, with subsequent dose adjustments to target iPTH levels of 150-300 pg/mL. Results: Of the 45 patients enrolled, 44 completed the study, with 20 patients in the Mild Group, 12 in the Moderate Group, and 12 in the Severe Group. The baseline iPTH level for the 44 patients was 655.05 (469.68, 831.40) pg/mL, which decreased to 269.90 (176.45, 365.65) pg/mL after 12 weeks of treatment. The overall mean percentage change in iPTH levels from baseline to week 12 was -55.45% ± 20.08%, with 86.4% of patients (38 cases) achieving a ≥30% reduction compared to baseline. At week 12, 80.00% of patients (16 cases) in the Mild Group had iPTH levels within the target range of 150-300 pg/mL or less than 150 pg/mL, compared to 41.76% (5 cases) in the Moderate Group and 33.33% (4 cases) in the Severe Group. All three groups showed a decrease in serum alkaline phosphatase (ALP) levels, with the Severe Group experiencing a statistically significant reduction (P = 0.001). The most common adverse event was hypercalcemia, occurring in 33.3% of patients (15 cases), with only 8.9% (4 cases) experiencing severe hypercalcemia (serum calcium >2.8 mmol/L). Hypercalcemia was resolved after dose reduction or discontinuation of the medication. Conclusion: https://www.chictr.org.cn/showproj.html?proj=187332, identifier ChiCTR2300073196.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, 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.
