DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for endometriosis — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEndometriosis maps to a 41-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
approvedDanazolApproved drug
Structures already discussed alongside endometriosis 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
The causes of endometriosis and the mechanisms of its development remain largely unknown, despite extensive investigation. A 2019 review states that all cases are thought to be initiated through a common pathophysiological mechanism involving downstream molecular pathways, but the specific triggers are not established. A 2021 review similarly notes that the etiology and pathophysiologic changes behind endometriosis and its potential role in endometrial cancer are still unclear. A 2022 transcriptome study of patients with normal, mild, and severe endometriosis identified genes with persistent expression dysregulation and predicted 792 drugs that interact with the targeted core genes, but this is computational prediction only, not clinical testing.
A 2012 systematic review of phenomics found that endometriosis is associated with specific phenotypic traits. A modest inverse correlation was observed between endometriosis and adult body mass index, and a stronger association was consistently demonstrated between endometriosis and early life body size, even after adjusting for age, birthweight, age at menarche, parity, and oral contraceptive use. A skin phenotype characterised by the presence of naevi and freckles and high sensitivity to sun exposure was represented more frequently in women with endometriosis.
A 2020 pilot study compared letrozole (2.5 mg/day) combined with oral contraceptives versus oral contraceptives alone in 820 women with endometriosis-related pain over six months of treatment. At completion of treatment, chronic pelvic pain intensity continued to decrease during treatment, and at one month after treatment it was significantly lower than at six-month follow-up and baseline in both groups. The mean pain score in the letrozole plus oral contraceptives group was 1.5 ± 1.4, versus 2.9 ± 1.2 in the oral contraceptives alone group. The intensity of chronic pelvic pain and deep dyspareunia was significantly decreased at both one month after treatment and six-month follow-up. The authors called the treatment a promising new modality warranting further investigation, but the study is a pilot, not a definitive trial.
What is still missing is a clear molecular target validated in human tissue, a large randomised controlled trial with longer follow-up and standardised pain measurement, and patient stratification by disease stage or phenotype. The 2022 drug prediction list of 792 compounds has not been tested in any clinical setting for endometriosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cochrane Database of Systematic Reviews · 2007 · 193 citations · open access
Danazol for pelvic pain associated with endometriosis
AbstractBACKGROUND: Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments for endometriosis aim to remove or decrease the deposits of ectopic endometrium. The observation that hyper androgenic states (an excess of male hormone) induce atrophy of the endometrium has led to the use of androgens in the treatment of endometriosis. Danazol is one of these treatments. The efficacy of danazol is based on its ability to produce a high androgen and low oestrogen environment (a pseudo menopause) which results in atrophy of the endometriotic implants and thus an improvement in painful symptoms. OBJECTIVES: To determine the effectiveness of danazol compared to placebo or no treatment in the treatment of the symptoms and signs, other than infertility, of endometriosis in women of reproductive age. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (searched April 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2007), and MEDLINE (1966 to April 2007). In addition, all reference lists of included trials were searched, and relevant drug companies were contacted for details of unpublished trials. SELECTION CRITERIA: Randomised controlled trials in which danazol (alone or as adjunctive therapy) was compared to placebo or no therapy. Trials which only reported infertility outcomes were excluded. DATA COLLECTION AND ANALYSIS: Only five trials met the inclusion criteria and two authors independently extracted data from these trials. All trials compared danazol to placebo. Three trials used danazol as sole therapy and three trials used danazol as an adjunct to surgery. Although the main outcome was pain improvement other data relating to laparoscopic scores and hormonal parameters were also collected. MAIN RESULTS: Treatment with danazol (including adjunctive to surgical therapy) was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were improved with danazol treatment (including as adjunctive therapy) when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than for placebo. AUTHORS' CONCLUSIONS: Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.
International Journal of Molecular Sciences · 2021 · 101 citations · open access
Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives
AbstractThe human endometrium is a unique tissue undergoing important changes through the menstrual cycle. Under the exposure of different risk factors in a woman's lifetime, normal endometrial tissue can give rise to multiple pathologic conditions, including endometriosis and endometrial cancer. Etiology and pathophysiologic changes behind such conditions remain largely unclear. This review summarizes the current knowledge of the pathophysiology of endometriosis and its potential role in the development of endometrial cancer from a molecular perspective. A better understanding of the molecular basis of endometriosis and its role in the development of endometrial pathology will improve the approach to clinical management.
Cochrane Database of Systematic Reviews · 2001 · 85 citations
Danazol for pelvic pain associated with endometriosis
AbstractBACKGROUND: Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments for endometriosis aim to remove or decrease deposits of ectopic endometrium. The observation that hyperandrogenic states (an excess of male hormone) induce atrophy of the endometrium has led to the use of androgens in the treatment of endometriosis. Danazol is one of these treatments used. The efficacy of danazol is based on its ability to produce a high androgen/low estrogen environment (a pseudo menopause) which results in the atrophy of endometriotic implants and thus an improvement in painful symptoms. OBJECTIVES: To determine the effectiveness of danazol compared to placebo or no treatment in the treatment of the symptoms and signs, other than infertility, of endometriosis in women of reproductive age. SEARCH STRATEGY: The Menstrual Disorders Group search strategy was used to identify randomised controlled trials of the use of danazol in endometriosis. In addition, all reference lists of included trials were searched, and relevant drug companies were contacted for details of unpublished trials SELECTION CRITERIA: Randomised controlled trials in which danazol (alone or as adjunctive therapy) was compared to placebo or no therapy. Trials which only reported infertility outcomes were excluded. DATA COLLECTION AND ANALYSIS: Only four trials met the inclusion criteria and two authors extracted data independently from these trials. All four trials compared danazol to placebo. Two trials used danazol as sole therapy and two trials used danazol as an adjunct to surgery. Although the main outcome was pain improvement other data relating to laparoscopic scores and hormonal parameters were also collected. MAIN RESULTS: Treatment with danazol (including adjunctive surgical therapy) was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were improved with danazol treatment (including adjunctive therapy) when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than placebo. REVIEWER'S CONCLUSIONS: Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.
AbstractBACKGROUND: Endometriosis has been associated with specific morphometric characteristics and pigmentary traits. The purpose of this study was to systematically review prior publications dealing with this aspect in order to revisit phenotypic information in the context of phenomics principles. METHODS: Comprehensive searches of Pubmed, Medline and Embase were conducted to identify studies, published from 1990 to 2011 in the English language literature, on the relationship between endometriosis and morphometric characteristics/pigmentary traits. RESULTS: We identified 11 studies on the association between endometriosis and body mass index (BMI) in the adult population and 5 studies on the same association during early life. While a modest inverse correlation was found between endometriosis and adult BMI, a stronger association was consistently demonstrated between endometriosis and early life body size, even after adjusting for confounding factors such as age, birthweight, age at menarche, parity and oral contraceptive use. Four papers have been published on the association between endometriosis and cutaneous naevi and five on the association between the disease and specific pigmentary traits. A skin phenotype characterized by the presence of naevi and freckles and by a high sensitivity to sun exposure is represented more frequently in women with endometriosis. CONCLUSIONS: Endometriosis appears to be associated with some phenotypic variations likely attributable to the strong effect of the environment on the expression and function of genes influencing the traits. Novel clues on endometriosis pathogenesis may derive from the analysis of the phenotypic traits associated with the disease.
Letrozole combined with oral contraceptives versus oral contraceptives alone in the treatment of endometriosis-related pain symptoms: a pilot study
AbstractBackground To compare the efficacy and the tolerability of letrozole combined with oral contraceptives versus oral contraceptives alone in treating endometriosis-related pain.Methods A total of 820 women with endometriosis presented with endometriosis-related pain were enrolled with this study. Patients were randomly treated either with letrozole (2.5 mg/day) combined with oral contraceptives (Desogestrel and Ethinylestradiol Tablets) or oral contraceptives (Desogestrel and Ethinylestradiol Tablets) alone for 6 months. Changes in pain symptoms during treatment and in 1 months after treatment, 6-month follow-up and 12-month follow-up were evaluated. Adverse effects of each treatment protocol were recorded.Results At completion of treatment, the intensity of chronic pelvic pain continued to decrease during treatment and at 1-month after treatment it was significantly lower than at 6-month follow-up and baseline level both in LE + oral contraceptives group (Mean ± SD,1.5 ± 1.4) and in oral contraceptives alone group(Mean ± SD,2.9 ± 1.2).The intensity of chronic pelvic pain and deep dyspareunia was significantly decrease at both 1-month after treatment and 6-month follow-up.Conclusions This treatment for endometriosis is a promising new modality that warrants further investigation.
Human Reproduction · 1996 · 15 citations · open access
Medical treatment of symptomatic endometriosis
AbstractThe concept of endometriosis and strategies for its treatment are reviewed. Treatment is mainly endocrine-based, using progestogens, danazol and luteinizing hormone-releasing hormone (LHRH) agonists. Such treatment is complex, and therapy strategies have to be tailored to the individual; the choice of treatment, therefore, depends on the metabolic and side-effects of each compound.
Fundamental and Clinical Medicine · 2019 · 5 citations · open access
Causes and mechanisms of endometriosis: an update
AbstractDespite extensive investigations, the causes of endometriosis and mechanisms of its development are largely unknown. Here we review the existing theories, analyzing the risk factors and triggers of endometriosis. We suggest that all cases of endometriosis are initiated through a common pathophysiological mechanism which involves all downstream molecular pathways.
Annals of Translational Medicine · 2022 · 1 citations · open access
Persistent dysregulation of genes in the development of endometriosis
AbstractBackground: Endometriosis is a chronic condition that affects women of child-bearing age. Since the etiology and pathogenesis of endometriosis have not been fully elucidated, it is important to investigate the mechanisms that lead to the deterioration of endometriosis. Methods: In this study, the transcriptome data of patients with normal, mild, and severe endometriosis were examined using the GSE51981 dataset obtained from the Gene Expression Omnibus database. Short Time Series Expression Miner (STEM) was used to screen the genes with continuous expression disorder in the development process, and the core genes were identified by constructing a protein-protein interaction network. The molecular mechanisms of endometriosis were examined using enrichment analysis. Finally, the transcription factors that regulate the core genes were predicted and the comprehensive mechanisms involved in the development of endometriosis were examined. Results: to participate in immune related signaling pathways. Drug prediction analysis identified 792 drugs that interact with the targeted core genes. Conclusions: This study explored the molecular mechanisms involved in the development of endometriosis and identified potential biomarkers of endometriosis. This data may provide novel targets and research directions for the diagnosis and treatment of endometriosis.
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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