DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 46,XY complete gonadal dysgenesis — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease module46,XY complete gonadal dysgenesis maps to a 13-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
approvedOxandroloneApproved drug
Structures already discussed alongside 46,xy complete gonadal dysgenesis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
aldo-keto reductase family 1 member C2 (AKR1C2) — AKR1C2 is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has ibuprofen bound in it, shown as sticks.
Loading structure…
helix sheet ibpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4JTR · 1.3 Å · ligand IBUPROFEN (IBP). Experimental structure, not a prediction.
What the evidence adds up to
In 46,XY complete gonadal dysgenesis, adult height is greater than in XX gonadal dysgenesis. A 1992 comparison of published cases found mean adult height in XYGD patients was 171.0 cm (SD 7.8, n = 27) versus 164.4 cm (SD 7.7, n = 27) in XXGD patients (p < 0.01). The authors interpreted this as evidence for a Y-specific growth gene acting independently of gonadal sex steroids.
One 1973 study of oxandrolone in nine girls with XO gonadal dysgenesis (Turner syndrome) reported that growth rate increased two- to eightfold over treatment periods of four to 34 months, with less osseous maturation than expected. Growth acceleration was greatest in the first year. Side effects were limited to voice change and pubic hair growth, and were not sufficient to stop treatment. No data exist for oxandrolone in 46,XY complete gonadal dysgenesis.
A 1988 endocrine investigation of a single 46,XY pure gonadal dysgenesis patient found high plasma gonadotrophins and low oestradiol before surgery. Streak gonads contained gonadoblastoma and dysgerminoma. Oestradiol benzoate initially suppressed then stimulated LH release without changing endogenous sex steroid levels. hCG injection failed to stimulate steroid secretion. In vitro, steroid-metabolising enzymes in dysgenetic gonadal tissue resembled ovarian tissue more than testes from androgen-insensitive patients, except that aromatase activity was higher in the dysgenetic gonads than in pre- or post-menopausal ovaries. Genital skin fibroblasts showed normal 3α/β- and 17β-hydroxysteroid dehydrogenase activities but low 5α-reductase activity; androgen binding was within the male control range.
A 2012 review states that 46,XY complete gonadal dysgenesis is diagnosed by clinical findings, gonadal histology, and chromosome analysis. Because of increased risk for gonadal tumours (most commonly dysgerminoma), abdominal streak gonads should be surgically removed. Hormone replacement therapy is required from puberty onward. What remains missing are prospective trials of any growth-promoting agent in this specific population, data on long-term outcomes beyond height, and any evidence that modifying growth or endocrine pathways alters tumour risk or quality of life.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Medical Genetics · 1992 · 53 citations · open access
Comparison of adult height between patients with XX and XY gonadal dysgenesis: support for a Y specific growth gene(s).
AbstractAdult height was compared between published cases of patients with XX gonadal dysgenesis (XXGD) and those with XY gonadal dysgenesis (XYGD). The mean adult height of XYGD patients (171.0 cm (SD 7.8), n = 27) was significantly greater than that of XXGD patients (164.4 cm (7.7), n = 27) (p less than 0.01). This finding supports the existence of a Y specific growth gene(s) which promotes statural growth independently of the effects of gonadal sex steroids.
Archives of Pediatrics and Adolescent Medicine · 1973 · 45 citations
Oxandrolone for Growth Promotion in Turner Syndrome
AbstractNine girls with XO gonadal dysgenesis have been treated for periods of four months to 34 months with oxandrolone. Growth rate increased twofold to eightfold over the entire period of treatment, with less osseous maturation than expected for either chronologic aging or statural age advance. Growth acceleration was greatest during the first year of treatment. Noticeable side effects were not sufficient to stop treatment and were limited to voice change and pubic hair growth.
IN‐VIVO AND IN‐VITRO ENDOCRINE INVESTIGATION OF PURE GONADAL DYSGENESIS
AbstractDiagnosis of XY pure gonadal dysgenesis was established in a patient of female phenotype, with female internal genitalia, but with a chromosomal constitution of 46 XY. Streak gonads had undergone neoplastic transformation--gonadoblastoma and dysgerminoma. Before operation the concentrations of gonadotrophins in plasma were high and of oestradiol was low. Administration of oestradiol benzoate initially suppressed and then stimulated an increase in the plasma concentration of LH. These changes were not accompanied by changes in blood levels of endogenous sex steroids. A single injection of hCG failed to stimulate steroid secretion. The activities in vitro of steroid-metabolizing enzymes in the dysgenetic gonadal tissue more closely resembled those of ovarian tissue from a premenopausal and from a postmenopausal women than those in testes from two androgen-insensitive patients. However, aromatase activity was higher in the dysgenetic gonads than in the pre or post-menopausal ovaries. Examination of enzymes in genital skin fibroblasts demonstrated normal activities of 3 alpha/beta-beta-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase (oxidative and reductive directions). However, 5 alpha-reductase activity was low in minces and fibroblasts of genital skin from the patient. Androgen binding was within the range for male controls.
Electronic Journal of General Medicine · 2012 · 1 citations · open access
46 XY Gonodal Dysgenesis
Abstract46,XY disorder of sex development (46,XY DSD) is characterized by a 46,XY karyotype, ambiguous genitalia with mild to severe penoscrotal hypospadias ,dysgenetic testes, reduced to no sperm production, and müllerian structures that range from absent to presence of a fully developed uterus and fallopian tubes. 46,XY complete gonadal dysgenesis is characterized by a 46,XY karyotype, normal female external genitalia, completely undeveloped streak gonads, no sperm production, and presence of normal müllerian structures and often not diagnosed until puberty when secondary sexual characteristics fail to develop. The diagnosis of 46,XY DSD and 46,XY gonodal dysgenesis relies on clinical findings, gonadal histology, chromosome analysis testing to detect changes in genes.Because of increased risk for gonadal tumors(most commonly dysgerminoma) abdominal streak gonads should be surgically removed . Typically, hormone replacement therapy (HRT) is required from puberty onward. Here we describe the clinical, endocrinological and molecular data of a patient with complete 46, XY gonadal dysgenesis.
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.
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.
