DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for hypothyroidism — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypothyroidism maps to a 42-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
approvedSunitinibApproved drugapprovedLevothyroxineApproved drug
Structures already discussed alongside hypothyroidism in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
TRANSTHYRETIN THR119MET PROTEIN STABILISATION — Levothyroxine has a real, experimentally solved structure in complex with this target (PDB 1F86, 1.1 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 t44drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1F86 · 1.1 Å · ligand Levothyroxine (T44). Experimental structure, not a prediction.
What the evidence adds up to
A 2009 study of 47 patients with subclinical hypothyroidism and 30 euthyroid controls found that the subclinical group had statistically significantly higher mean platelet volume and platelet distribution width values (p<0.001 for both). The authors concluded these platelet parameters play an important predictive role in subclinical hypothyroidism. A 2016 review notes that subclinical hypothyroidism has a prevalence of 4–20% depending on population, and that while epidemiological analysis associates it with increased cardiovascular risk, clinical practice guidelines express uncertainty about whether to monitor or treat. The review states that large-scale, well-designed randomised clinical trials regarding treatment of subclinical hypothyroidism are still awaited.
A 2015 study of 81 patients with metastatic renal cell carcinoma treated with sunitinib found that 30 patients (37%) developed hypothyroidism within a median of 3 months. Among those who became hypothyroid, the objective remission rate was 46.7% versus 13.7% in euthyroid patients (p=0.001). Median progression-free survival was 17 months in hypothyroid patients versus 10 months in euthyroid patients (p=0.001). Median overall survival was 39 months in hypothyroid patients versus 20 months in euthyroid patients (p=0.019). The authors concluded that hypothyroidism during sunitinib treatment was significantly associated with longer progression-free survival, overall survival, and better objective response rate.
A 2020 in silico study examined five genes involved in congenital hypothyroidism—NIS, PAX8, DUOX2, FOXE1, NKX2-1—using bioinformatics tools. The authors reported that the genes showed consensus sequence motifs and that phylogenetic trees revealed sub-clusters with high protein homology. A 1969 journal article on hypothyroidism from the British Journal of Dermatology provides no data or results.
What is still missing: adequately powered randomised trials to determine whether treating subclinical hypothyroidism reduces cardiovascular events; prospective studies validating platelet parameters as clinical predictors; and any drug repurposing data for hypothyroidism itself—the sunitinib finding is about a drug-induced side effect in cancer, not a treatment for hypothyroidism.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Thyroid · 2010 · 71 citations
Sunitinib Induces Hypothyroidism with a Markedly Reduced Vascularity
AbstractBACKGROUND: Sunitinib is a small molecule that inhibits receptor tyrosine kinases, including the vascular endothelial growth factor receptors, and exhibits antiangiogenic and antitumor activity. This molecule has also been reported to cause hypothyroidism at a high frequency, but the mechanism of this is unknown. SUMMARY: A 60-year-old woman was administered sunitinib for the treatment of metastatic renal cell carcinoma. One week later, she displayed overt hypothyroidism with an atrophic thyroid and a marked reduction in vascularity as determined by ultrasonography, despite high levels of thyrotropin. In contrast, during the off-periods in the sunitinib treatment cycles, the volume of her thyroid recovered with an increase in vascularity despite a low level of thyrotropin. These results suggest that thyroid function and volume may depend on the vascularity, which is negatively regulated by sunitinib. CONCLUSION: Our case study provides compelling evidence that sunitinib induces hypothyroidism by reducing blood flow via capillary regression and constriction.
The effect of subclinical hypothyroidism on platelet parameters
AbstractBACKGROUND: Hypothyroidism has a broad clinical spectrum. Today, physicians frequently encounter patients with very mild thyroid dysfunction instead of overt hypothyroidism. These patients have normal serum levels of thyroxine and triiodothyronine and only mildly elevated serum thyrotropin levels. Such patients are often identified through routine screening or in the course of an evaluation of common nonspecific symptoms. On the other hand, coronary heart disease is the leading cause of death in developed countries. There are studies, which suggest platelets play a role in the pathogenesis of atherosclerosis and coronary heart disease. AIM: The aim of this study is to compare the platelet count and other platelet parameters in subclinical hypothyroidic and euthyroidic healthy control group and to investigate whether these parameters have a predictive significance in patients with subclinical hypothyroidism. MATERIALS AND METHODS: Forty-seven patients with subclinical hypothyroidism and 30 euthyroidic healthy control group were enrolled into the study. RESULTS: Patients with subclinical hypothyroidism had higher mean platelet volume (MPV) and platelet distribution width (PDW) values than control group, which were statistically significant (p<0.001 and p<0.001), respectively. CONCLUSION: Our results indicate that MPV and PDW play an important predictive role in subclinical hypothyroidism.
Acta Oncologica · 2013 · 35 citations · open access
Risk of hypothyroidism in patients with cancer treated with sunitinib: A systematic review and meta-analysis
AbstractBACKGROUND: The multitargeted tyrosine kinase inhibitor sunitinib is used in various cancers. Clinical studies have reported a substantial variation in the incidence of hypothyroidism associated with sunitinib, without a systemic attempt to synthesize these data. METHODS: We searched Medline databases for relevant clinical trials published up to May 2012. Phase II and III trials and expanded access programs of sunitinib in patients with any type of cancer that reported occurrence of hypothyroidism were eligible. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the heterogeneity of included studies. RESULTS: Incidence analysis was performed using 6678 sunitinib-treated patients from all 24 eligible trials. The incidence of all- and high-grade hypothyroidism was 9.8% (95% CI 7.3-12.4%) and 0.4% (95% CI 0.3-0.5%), respectively. A meta-analysis of seven randomized trials with 2787 subjects revealed a RR of all- and high-grade hypothyroidism of 13.95 (95% CI 6.91-28.15; p < 0.00001) and 4.78 (95% CI 1.09-20.84; p = 0.04), respectively. Subgroup analysis revealed a significantly higher incidence of all-grade hypothyroidism in patients receiving sunitinib for longer duration than in patients receiving sunitinib for shorter duration (p = 0.02). CONCLUSIONS: This meta-analysis of data available from clinical trials demonstrates that sunitinib is associated with a significant risk of developing all- and high-grade hypothyroidism. These data provide further evidence to recommend monitoring for hypothyroidism in patients receiving sunitinib.
Is sunitinib-induced hypothyroidism a predictive clinical marker for better response in metastatic renal cell carcinoma patients?
AbstractBACKGROUND: The main goal of this study was to examine whether the occurrence of hypothyroidism during sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. METHODS: The study enrolled 81 patients with pathologically proven mRCC who were treated with sunitinib between March 2008 and June 2013.Thyroid function evaluation comprised (free-thyroxine) FT4 and thyroid-stimulating hormone (TSH) before treatment and at day 1 of each 6-week cycle. Survival analysis was performed using the Kaplan-Meier method, and the differences among the groups were determined using the log-rank test. RESULTS: Hypothyroidism occurred in 30 (37%) of 81 patients within a median 3 months (range 1-18) of treatment initiation. There was a statistically significant correlation between the occurrence of hypothyroidism during treatment and the rate of objective remission (ORR) (hypothyroid patients vs euthyroid patients: 46.7 vs 13.7%, respectively; P = 0.001). Median progression-free survival (PFS) was 10 (95% CI 6.13-13.8) months in the euthyroid patients, and 17 (95% CI 9.33-24.6) months in the hypothyroid patients (P = 0.001). The median overall survival (OS) was 39 (95% CI 25.4-52.5) months in the hypothyroid patients and 20 (95% CI 14.7-25.2) months in the euthyroid patients (P = 0.019). CONCLUSIONS: The occurrence of hypothyroidism during treatment in patients was significantly associated with longer PFS, OS and better ORR in the current study.
touchREVIEWS in Endocrinology · 2016 · 10 citations · open access
Subclinical Hypothyroidism – What is Responsible for its Association with Cardiovascular Disease?
AbstractSubclinical hypothyroidism (SH) is a common condition, with prevalence estimates ranging from 4-20%, depending on the population demographics. Although epidemiological analysis associates it with an increased risk of cardiovascular disease, clinical practice guidelines express uncertainty about whether to monitor or to treat. As we await large-scale, well-designed randomised clinical trials regarding treatment of SH, a review of pathophysiological considerations may be informative to better understand this disorder.
Journal of the Pakistan Medical Association · 2020 · 1 citations · open access
Insilico study of genes involved in Congenital Hypothyroidism.
AbstractOBJECTIVE: To study the orthologs of the five genes of congenital hypothyroidism NIS, PAX8, DUOX2, FOXE1, NKX2-1 that are involved in the development of the thyroid gland. METHODS: The study was conducted at INMOL Cancer Hospital, Lahore in September 2017 and comprised of finding gene orthologs, phylogenetic tree and domains of NIS, PAX8, DUOX2, FOXE1, NKX2-1 which were studied using different bioinformatics tools, including FASTA, BLAST, ENSEMBL, UniProt, MultiAlin, to find out the important domains involved in the mutations of these genes. RESULTS: Genes showed consensus sequence / motifs involved in congenital hypothyroidism. Phylogenetic results showed that these genes shared some common motifs. Phylogenetic trees revealed sub-clusters with high protein homology. CONCLUSIONS: Genes involved in congenital hypothyroidism were found to have a consensus sequence motifs.
British Journal of Dermatology · 1969 · 0 citations
HYPOTHYROIDISM
AbstractJournal Article HYPOTHYROIDISM Get access J. A. Milne J. A. Milne Department of Dermatology University of Glasgow Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 12, 1 December 1969, Pages 937–938, https://doi.org/10.1111/j.1365-2133.1969.tb15976.x Published: 01 December 1969
The efficacy of levothyroxine in the treatment of subclinical hypothyroidism
AbstractObjective To explore the efficacy of levothyroxine for the treatment of subclinical hypothyroidism.Methods 100 patients with subclinical hypothyroidism who had been treated in our hospital during the period of February 2010 to September 2012 were randomly selected.Various indexes and the efficacy were analyzed after treatment.Results After treatment with levothyroxine,the clinical symptoms improved significantly in the patients,and the indexes differed significantly,with a statistical difference (P＜0.05).Conclusions Levothyroxine is efficacious in the treatment of subclinical hypothyroidism.It can effectively prevent deterioration of the condition and normalize FT3,FT4,and TSH.
Key words:
Levothyroxine; Hypothyroidism; Efficacy
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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