DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for adenomyosis — screening already-approved drugs against its 9-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAdenomyosis maps to a 9-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
Structures already discussed alongside adenomyosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Sex Hormone-binding globulin mutant E176K — Danazol has a real, experimentally solved structure in complex with this target (PDB 6ULB, 1.75 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 qa1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ULB · 1.75 Å · ligand Danazol (QA1). Experimental structure, not a prediction.
What the evidence adds up to
In a 2008 mouse model of adenomyosis, an intrauterine device loaded with danazol reduced the number of adenomyosis nodules. Thirty ICR mice were grafted with a single pituitary gland to induce the condition. After two months of treatment, the nodule number decreased significantly only at the highest danazol dose tested (2.0 mg per 20 g body weight, P = 0.002). Plasma danazol concentrations with intrauterine delivery were low and stable compared with oral administration. The authors concluded that human trials were warranted. No human data on danazol-loaded intrauterine devices for adenomyosis are provided in these abstracts.
A 2017 study examined Nrf2 protein expression in tissue samples from women with adenomyosis. Nrf2 protein levels were significantly higher in eutopic and ectopic endometrial glands compared with controls (p < 0.05), but Nrf2 mRNA levels showed no statistical difference. In primary cultured endometrial glandular cells, an Nrf2 agonist increased cell migration speed and MMP9 protein levels, while Nrf2 siRNA reduced both. The authors suggested that reducing Nrf2 expression could be a new therapeutic target. No drug or clinical intervention was tested in that study.
A 2014 abstract states that diffuse adenomyosis is difficult to diagnose and treat, that no gold standard for organ-preserving therapy has been established, and that MRI-guided focused ultrasound (MRgFUS) might be a promising technology. No results from any MRgFUS trial are reported in the abstract. A 2023 abstract reports that acetyl-CoA acetyltransferase 1 expression is decreased in adenomyosis tissue compared with eutopic endometrium and control tissue, and suggests this may be associated with the molecular pathogenesis. A 2021 review notes that the etiology of adenomyosis remains under investigation, that none of the existing theories fully explain its development, and that some investigators describe malignant transformation of adenomyosis.
What is still missing: no randomised controlled trials of any drug or device for adenomyosis in humans are presented here. The danazol-loaded intrauterine device has only been tested in mice. The Nrf2 finding is preclinical and not yet translated into a therapy. No large-scale, well-powered clinical trial with standardised outcome measures (pain, bleeding, fertility) is described. Patient stratification by disease subtype (focal versus diffuse) or by molecular markers is absent from these abstracts. Funding for human trials and a consensus on clinically meaningful endpoints remain lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Reproduction · 2008 · 29 citations
Evaluation of the efficacy of a danazol-loaded intrauterine contraceptive device on adenomyosis in an ICR mouse model
AbstractBACKGROUND: Danazol, a synthetic steroid with antigonadotrophic properties, has been widely used for the treatment of endometriosis and adenomyosis. However, the local application of danazol to the uterus to treat adenomyosis is controversial. The objective of this study is to develop an effective treatment for adenomyosis using danazol via intrauterine contraceptive device (IUCD) delivery. METHODS: An adenomyosis animal model was established using Institute for Cancer Research, Swiss-derived (ICR) mice, grafted with a single pituitary gland (n = 30). Four months after grafting, IUCDs with three different quantities of danazol were prepared and used to treat the ICR mice with adenomyosis. After 2 months of treatment with a danazol-loaded IUCD, the number of adenomyosis nodules and the hematoxylin-eosin staining scores were measured and compared with mice given daily oral danazol and controls (no adenomyosis). RESULTS: As the danazol dose increased, the nodule number decreased reaching significance at a dose of 2.0 mg per 20 g body weight (P = 0.002). When compared with oral administration, the plasma danazol concentrations with IUCD delivery were low and stable. CONCLUSIONS: These results suggest that an IUCD loaded with an appropriate dose of danazol may be an effective treatment for adenomyosis and that human trials are warranted.
Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis
AbstractOBJECTIVE: To explore the expression level of Nrf2 in adenomyosis and study the mechanism of abnormal expression of Nrf2 in the pathogenesis of adenomyosis. METHODS: Western blot, immunohistochemistry(IHC) and real time PCR were used to measure Nrf2 expression levels in tissue and cell samples. Knockdown and overexpression of Nrf2 were used to investigate the variation of migration ability of endometrial glandular cells as well as the regulatory mechanism. RESULTS: Nrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods. (p< 0.05). However, there was no statistical difference in Nrf2 mRNA expression levels between the adenomyosis and control groups. Using an agonist and Nrf2 siRNA, we regulated the Nrf2 protein levels of primary cultured endometrial glandular cells. With increased expression of Nrf2, cell scratch assay showed that the agonist-treated group migrated significantly faster than the control group, with MMP9 protein level markedly elevated. In contrast, Nrf2 siRNA-treated group migrated slower than the control group, with decreased expression of MMP9 protein. All of the scratching healing spaces and protein levels between the treated and control groups were statistically significant (p< 0.05). CONCLUSIONS: Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis. Specified reduction of Nrf2 expression could prove to be a new therapeutic target in the clinical treatment of adenomyosis.
Journal of Therapeutic Ultrasound · 2014 · 3 citations · open access
MRI-guided focused ultrasound (MRgFUS) surgery in conserving therapy of adenomyosis
AbstractBackground Adenomyosis is a complex disorder that accounts up to one third of gynecological morbidity. Diffuse form of adenomyosis is most difficult to diagnose and treat. All attempts to create a “gold standard” in preserving therapy have not been successful so far. MRgFUS could be a promising technology for organ-preserving treatment of this disease. Purpose of this study was to determine the efficacy of MRgFUS ablation in organ-preserving treatment of adenomyosis.
Journal of Turkish Society of Obstetric and Gynecology · 2023 · 3 citations · open access
Role of acetyl-CoA acetyltransferase 1 expression in the molecular mechanism of adenomyosis
AbstractObjective: in the development and molecular mechanism of adenomyosis. Materials and Methods: gene were determined by the reverse transcription-polymerase chain reaction method. Results: in adenomyosis tissue is decreased compared with both eutopic endometrium and control groups tissues. Conclusion: may be associated with the molecular pathogenesis of adenomyosis.
AbstractAdenomyosis have an extremely negative impact on a woman's reproductive health. In the absence of drug therapy, the likelihood of surgical treatment increases which could be very traumatic for the patient and lead to a decline in infertility and onset of early menopause. That is why it is extremely important to start therapy in a timely manner, the most important method of which is hormonal treatment. The article discusses the efficacy and safety profiles of progestin dienogest.
EXPERIMENTAL & CLINICAL MEDICINE GEORGIA · 2021 · 0 citations · open access
PROBLEMATIC ISSUES IN THE ETIOLOGY AND PATHOGENESIS OF ADENOMYOSIS
AbstractNowadays, adenomyosis represents one of the most common pathology of female genital system. It occurs at different ages, including nulliparous, infertile and multiparous women. The etiology of adenomyosis is still under investigation. Despite the fact that there are many different theories, none of them fully explain the mechanisms of adenomyoisis development. The pathogeneis of adenomyosis is also less studied. Many studies indicate the involvement of female sex hormone receptors, cell proliferation and apoptosis, as well as the involvement of inflammation. Some investigators describe the malignant transformation of adenomyosis, which makes the study of the disease etiology and pathogenesis more important. In current review, we discuss the different theories of adenomyosis development, as well as the risk of malignant transformation.
Medical treatment of adenomyosis: a literature review
AbstractAdenomyosis is a heterogeneous gynecologic disease with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhea. This article provides an overview of current knowledge about the methods of medical therapy for adenomyosis, based on the current understanding of the pathogenesis of the disease. We searched for scientific publications in the Cochrane Library, PubMed, and eLIBRARY databases using the keywords "adenomyosis", "medical treatment", and "hormonal therapy" from 2017 to 2022. We analyzed and summarized the scientific data accumulated to date on the methods of medical treatment of adenomyosis in women of reproductive age using gonadotropin-releasing hormone agonists, aromatase inhibitors, mifepristone, a levonorgestrel-releasing intrauterine device, combined oral contraceptives, and progestins.
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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