DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for nontoxic goiter — screening already-approved drugs against its 36-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNontoxic goiter maps to a 36-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 nontoxic goiter 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
inositol-tetrakisphosphate 1-kinase (ITPK1) — ITPK1 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Q7D · 1.6 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
A 2016 case report describes a 47-year-old Japanese woman with a large multinodular goiter weighing 209 g, resected by total thyroidectomy, who carried a germline heterozygous KEAP1 mutation (c.1448 G>A, p.R483H). Nuclear accumulation of NRF2 was markedly higher in her nodules than in nodules from four unrelated patients with multinodular goiters. The authors conclude the KEAP1 gene was associated with development of a non-toxic multinodular goiter, but this is a single-patient finding with no functional validation beyond NRF2 staining.
A 2017 clinical study randomised 72 patients with multinodular or diffuse goiter to either the traditional Chinese medicine regimen Xing Qi Hua Ying Tang (XQHYT, n=36) or a control herbal decoction Hai Zao Yu Hu Tang (n=36), given twice daily for two 3-month courses. Symptom scores were lower in the treatment group (8.26 ± 2.62 vs 10.02 ± 2.62, p<0.05). Substantial goiter size reduction was reported in 82.3% of XQHYT-treated patients versus 67.7% of controls, and the overall effective rate was 91.2% versus 67.7% (p<0.05). Thyroid hormone levels remained normal in both groups. The study is small, single-centre, and uses subjective Chinese medicine symptom criteria; no blinding or placebo control is described.
A 1959 historical review notes David Marine's 1924 statement that simple goiter is the easiest and cheapest of all known diseases to prevent, but the abstract ends with Marine being forced to conclude something thirty years later, the content of which is not provided. No efficacy data from that review are given.
The remaining abstracts are not relevant to goiter treatment. A 2011 phase II trial of gemcitabine, oxaliplatin, and cetuximab in advanced pancreatic cancer enrolled 41 evaluable patients, with an overall response rate of 24%, median progression-free survival of 6.9 months, and median overall survival of 11.3 months; the authors concluded the regimen did not significantly extend PFS and should not be developed further. A 2020 zebrafish study examined graphene oxide toxicity and found functionalisation with Pluronic F127 reduced toxicity in a concentration- and size-dependent manner. A 1957 paper describes preparation of Neisseria gonorrhoeae endotoxin. A 2018 case report describes bottle gourd juice toxicity causing multiorgan dysfunction in one patient. A 2022 case report describes phenibut intoxication and withdrawal treated with baclofen.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Endocrinology · 2016 · 24 citations · open access
A Novel Germline Mutation of KEAP1 (R483H) Associated with a Non-Toxic Multinodular Goiter
AbstractBACKGROUND: gene was reported as a novel genetic abnormality associated with familial multinodular goiter. That report was limited, and the pathogenic features were not well established. PATIENT FINDINGS: We report a 47-year-old Japanese woman who presented with hyperthyroidism and a large multinodular goiter. The family history was notable for a paternal history of goiter. Graves' disease was diagnosed based on positive TRAb, but scintiscan imaging showed that the patient's radioiodine uptake was restricted in the non-nodular areas, indicating largely cold nodules. A total thyroidectomy was performed. The resected thyroid tissue weighed 209 g, and subsequent pathological findings were benign. The patient had a germline heterozygous KEAP1 mutation, c. 1448 G > A, resulting in an amino acid substitution (p.R483H). A next-generation sequencing analysis covering all known genes associated with multinodular goiter showed no additional germline mutation. The nuclear accumulation of NRF2, a protein associated with KEAP1, was shown at much higher rates in the patient's nodules compared with nodules obtained from four unrelated patients with multinodular goiters. CONCLUSION: gene was associated with the development of a non-toxic multinodular goiter.
American Journal of Clinical Oncology · 2011 · 21 citations
Phase II Study of Gemcitabine, Oxaliplatin, and Cetuximab in Advanced Pancreatic Cancer
AbstractOBJECTIVE: Little progress has been made in the treatment of pancreatic cancer (PC). This study evaluated the clinical activity of gemcitabine, oxaliplatin, and cetuximab (GOC) in patients with locally advanced or metastatic PC. METHODS: The study primary endpoint was progression-free survival (PFS). Eligible, chemotherapy-naive PC patients were treated with gemcitabine (1000 mg/m(2) over 100 min) on day 1, oxaliplatin (100 mg/m(2)) on day 2, every 2 weeks, and weekly cetuximab, (loading dose of 400 mg/m(2) on cycle 1 day 1 and 250 mg/m(2) thereafter). It was expected that GOC treatment would extend the median PFS from 5.8 to 7.54 months, a relative increase of 30%, compared with gemcitabine and oxaliplatin (historical control). RESULTS: A total of 41 evaluable patients were enrolled. The overall response rate was 24%. Median PFS time was 6.9 months and median overall survival (OS) was 11.3 months. Patients with locally advanced disease had longer median PFS (12.4 vs. 4.7 mo) and OS (15.7 vs. 6.4 mo) compared with patients with metastatic disease. The most common grade 3 to 4 toxicities included neutropenia (32%), infection (with normal or grade 1 to 2 neutropenia, in 24%), neuropathy (17%), fatigue (15%), and rash (7%). Five patients (12%) discontinued study treatment without evidence of progression. Rash was not a significant prognostic factor affecting PFS or OS. CONCLUSIONS: GOC is a feasible combination with an acceptable toxicity profile. However, GOC did not significantly extend PFS in the overall patient population to consider it for further development.
International Journal of Nanomedicine · 2020 · 18 citations · open access
<p>Synthesis, Characterization, and Toxicity Assessment of Pluronic F127-Functionalized Graphene Oxide on the Embryonic Development of Zebrafish (<em>Danio rerio</em>)</p>
AbstractBACKGROUND: In the current literature, there are ongoing debates on the toxicity of graphene oxide (GO) that demonstrate contradictory findings regarding its toxicity profile. As a potential drug carrier, these findings are very concerning due to the safety concerns in humans, as well as the dramatic rise of GO being excreted into the environment. Therefore, there is an imperative need to mitigate the potential toxicity of GO to allow for a safer application in the future. PURPOSE: The present study aims to address this issue by functionalizing GO with Pluronic F127 (PF) as a means to mitigate toxicity and resolve the biocompatibility of GO. Although results from previous studies generally indicated that Pluronic functionalized GO exhibits relatively low toxicity to living organisms, reports that emphasize on its toxicity, particularly during embryonic developmental stage, are still scarce. METHODS: In the present study, two different sizes of native GO samples, GO and NanoGO, as well as PF-functionalized GO, GO-PF and NanoGO-PF, were prepared and characterized using DLS, UV-Vis, Raman spectroscopy, FTIR, and FESEM analyses. Toxicological assessment of all GO samples (0-100 µg/mL) on zebrafish embryonic developmental stages (survival, hatching and heart rates, and morphological changes) was recorded daily for up to 96 hours post-fertilization (hpf). RESULTS: The toxicity effects of each GO sample were observed to be higher at increasing concentrations and upon prolonged exposure. NanoGO demonstrated lower toxicity effects compared to GO. GO-PF and NanoGO-PF were also found to have lower toxicity effects compared to native GO samples. GO-PF showed the lowest toxicity response on zebrafish embryo. CONCLUSION: These findings highlight that toxicity is dependent on the concentration, size, and exposure period of GO. Functionalization of GO with PF through surface coating could potentially mitigate the toxicity effects of GO in embryonic developmental stages, but further investigation is warranted for broader future applications.
Experimental Biology and Medicine · 1957 · 15 citations
Preparation and Some Properties of Neisseria gonorrhoeae Endotoxin.
Abstract1. An improved method for large scale cultivation of N. gonorrhoeae in an atmosphere of air has been described. 2. A rapid method for the preparation of a stable fraction containing dry, soluble gonococcus endotoxin and some of the properties of this product have been presented. This endotoxin appears to be a protein. 3. DNA equivalents in different gonococcus fractions do not parallel toxicity.
The Journal of Alternative and Complementary Medicine · 2017 · 11 citations
Treatment of Goiter with Traditional Chinese Medicine Regimen Xing Qi Hua Ying Tang: A Clinical Study on 72 Patients with Multinodular and Diffuse Goiter
AbstractOBJECTIVE: The present work aimed to further explore the therapeutic potential of Xing Qi Hua Ying Tang (XQHYT) by conducting a systemic clinical study in patients with goiter. DESIGN: Seventy-two patients with either multinodular or diffuse goiter were enrolled and randomly assigned into treatment group receiving XQHYT (n = 36) and control group receiving Hai Zao Yu Hu Tang (n = 36). LOCATION: Traditional Chinese Medicine Hospital of Shanxi. SUBJECTS: Patients were diagnosed multinodular goiter or diffuse goiter resulting from Qi stagnation. INTERVENTION: All patients took the extract twice a day (100 mL each time) for two courses of treatment, of which a single course lasted for 3 months. Before the treatment was commenced and after the completion of the treatment, general body checks, thyroid function test, and goiter size examination were performed. OUTCOME MEASURES: Scoring of the clinical symptoms using Chinese medicine symptomatology was also done. RESULTS: The symptom score of the treatment group was significantly lower than that of the control group (treatment group, 8.26 ± 2.62; control group, 10.02 ± 2.62; p < 0.05). Substantial reduction in goiter size was seen in 82.3% of XQHYT-treated patients, whereas in the control group only 67.7% of patients exhibited constricted goiter. When assessed by both the Chinese medicine criteria and goiter size, the overall effective rate of the treatment group was 91.2%, whereas that of the control group was only 67.7%. The difference was statistically significant (p < 0.05). XQHYT did not affect the normal functions of liver, kidney, and heart. For both groups of patients, their levels of thyroid-stimulating hormone, free T4 and free T3 were normal before the treatment, and were not affected by the treatment. CONCLUSION: XQHYT was shown to be a promising therapeutic regimen for the treatment of goiter. The herbal regimen ameliorated clinical symptoms of patients that were accompanied with reduction in the size of goiter.
Archives of Internal Medicine · 1959 · 0 citations
An Outline of the Use of Iodine in Endemic Goiter
AbstractThis section, which has as its primary purpose a review of the contributions of medical investigators and observers of the past to the present-day concepts of disease, is under the special editorship of Dr. Arthur Bloomfield, 2398 Sacramento St., San Francisco 15. His editorial in the August, 1957, issue of theA. M. A.Archives of Internal Medicine,gives further detail of what it is hoped to accomplish in these articles. Contributions or comments for this section may be sent directly to Dr. Bloomfield, or to the Chief Editor for transmittal to him. In 1924, seventeen years after his first experiments on the pathogenesis of goiter, David Marine wrote1: Simple goiter is the easiest and cheapest of all known diseases to prevent and its control may be accomplished by available methods as soon as organized society determines to make the effort. Thirty years later, he was forced to conclude
Indian Journal of Emergency Medicine · 2018 · 0 citations · open access
A Rare Entity of Bottle Gourd Toxicity with Multiorgan Dysfunction Syndrome
AbstractA 59 years old male was presented to our Emergency Department with complaints of multiple episode of vomiting and fresh blood in vomitus, loose stools and reddish coloured urine after consuming some home made bottle gourd juice. Later he was diagnosed as bottle gourd toxicity with a shock which led to MODS. He was aggressively managed with IV fluids, pantoprazole infusion, antibiotics and other supportive medications. He improved and was discharged in a stable condition after 7 days of hospitalization.
Saudi Journal of Medicine · 2022 · 0 citations · open access
The “Smart Pill” High: A Case of Phenibut Intoxication and Withdrawal
AbstractPhenibut is an anxiolytic and nootropic drug, discovered in the Soviet Union used to treat several psychiatric disorders. Currently it is available online as supplement. The case report highlights the abuse potential of phenibut, with the associated clinical presentation of intoxication, withdrawal, and relapse, as well as the use of baclofen as a potential treatment of phenibut withdrawal.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, 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.
