DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for androgen insensitivity syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAndrogen insensitivity syndrome maps to a 2-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 androgen insensitivity syndrome 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
androgen receptor (AR) — AR 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.
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helix sheet 1r,2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5CJ6 · 2.07 Å · ligand 2-chloro-4-{[(1R,2R)-2-hydroxy-2-methylcyclopentyl]amino}-3-methylbenzonitrile (51Y). Experimental structure, not a prediction.
What the evidence adds up to
The three abstracts describe androgen insensitivity syndrome as a condition caused by inactivating mutations in the androgen receptor gene, resulting in a female phenotype in individuals with a 46,XY karyotype. A 1997 review summarises that defects in androgen receptor function produce a spectrum of phenotypes, and that new molecular techniques had improved diagnosis, including prenatal diagnosis. A 2019 case report identifies a novel de novo c.1669_1670insC insertion in the AR gene in a patient with normal female external genitalia. A 2025 case report of Han Chinese twin girls describes one twin diagnosed at age 18 with complete androgen insensitivity syndrome, who had a vagina and breasts but no uterus or ovaries, underwent bilateral gonadectomy, and received hormone replacement therapy; pathological diagnosis showed immature testicular tissue development.
A 2022 multicentre, randomised, double-blind, double-dummy crossover trial investigated metabolic effects of estradiol versus testosterone replacement therapy in individuals with complete androgen insensitivity syndrome. The trial found no major differences in metabolic and safety parameters between the two treatments. This is described as the first study investigating these different treatment options in complete androgen insensitivity syndrome.
No abstract reports any drug that reverses or corrects the underlying androgen receptor defect. No abstract provides data on survival, response rates, or sample sizes for any therapeutic intervention beyond the 2022 crossover trial. The 2025 case report states that continuing hormone replacement therapy after gonadectomy is critical, and that patients' psychological difficulties should be addressed, but this is clinical management advice, not evidence of efficacy for any drug.
What is still missing is any trial of a drug that restores androgen receptor function, any large-scale randomised trial comparing hormone replacement regimens with adequate power to detect differences in long-term outcomes, and any validated method for stratifying patients by specific AR mutation type to guide therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 1997 · 51 citations
Molecular Biology and Function of the Androgen Receptor in Genital Development
AbstractPURPOSE: The rapidly growing field of molecular biology has caused exponential growth in our knowledge of the processes of embryogenesis. Since the cloning of the androgen receptor gene in 1988, investigators have been able to clarify many of the molecular events of male sexual differentiation that are mediated through the androgen receptor. We reviewed the current state of knowledge of the androgen receptor and its role in male genital development. MATERIALS AND METHODS: An intensive literature search was conducted to review reports on the androgen receptor and sexual differentiation since 1988. This review also includes ongoing research from our laboratory on the role of the androgen receptor in human genital development, as well as collaboration with other investigators. RESULTS: We reviewed the basic molecular biology of androgenic action mediated through the androgen receptor. This information has been integrated into the current understanding of human male sexual differentiation to clarify how androgens virilize the undifferentiated embryo. Defects in function of the androgen receptor may be manifested as a spectrum of phenotypes of the androgen insensitivity syndrome, and these phenotypes of male pseudohermaphroditism have been reviewed on a clinical and molecular basis. New molecular techniques have augmented the evaluation and diagnosis of the androgen insensitivity syndrome, and some groups have successfully diagnosed the condition prenatally. CONCLUSIONS: Basic scientific research of androgen receptor function and its role in male sexual development has provided a clearer understanding of the mechanisms responsible for the spectrum of defects secondary to the androgen insensitivity syndrome. This knowledge will enable clinicians to offer more accurate diagnosis and insightful counseling to affected patients and their families.
Journal of Human Reproductive Sciences · 2014 · 4 citations · open access
Laparoscopic gonedectomy in a case of complete androgen insensitivity syndrome
AbstractComplete Androgen insensitivity syndrome is a disorder of hormone resistance characterized by a female phenotype in an individual with an XY karyotype. The pathogenesis of CAIS involves a defective androgen receptor gene located on X-chromosome at Xq11-12and end organ insensitivity to androgens, although androgen concentrations are appropriate for the age of the patient. There are three major types of androgen insensitivity syndrome: Complete androgen insensitivity syndrome, minimal androgen insensitivity syndrome, and partial androgen insensitivity syndrome. Management of androgen insensitivity syndrome includes multidisciplinary approach and involves gonedectomy to avoid gonadal tumors in later life. Hormone replacement therapy (HRT) and psychological support are required in long-term basis.
Journal of Pediatric and Adolescent Gynecology · 2019 · 1 citations · open access
Novel Androgen Receptor Gene Variant Containing a Premature Termination Codon in a Patient with Androgen Insensitivity Syndrome
AbstractBACKGROUND: Androgen receptor (AR) mutations, which cause androgen insensitivity syndrome, impair the actions of 5α-dihydrotestosterone and testosterone, resulting in abnormal sexual development. In most cases, genetic aberrations of the AR are caused by substitutions, but also can result from mutations in splicing regions and deletions in the AR gene. CASE: Our present report describes a female patient with 46,XY karyotype and normal female external genitalia. A novel de novo c.1669_1670insC insertion in the AR gene caused androgen insensitivity syndrome. SUMMARY AND CONCLUSION: This report provides a detailed clinical characterization of the patient and a possible pathogenic mechanism leading to androgen insensitivity syndrome and should be particularly useful in genetic counseling.
Journal of Medical Case Reports · 2025 · 1 citations · open access
Complete androgen insensitivity syndrome in twins with discordant phenotypes: a case report and review of the literature
AbstractBACKGROUND: Complete androgen insensitivity syndrome is caused by inactivated mutations in the androgen receptor gene, which results in complete androgen resistance and a female phenotype with a 46,XY karyotype. This condition is rare in twins. CASE PRESENTATION: We report on a Han Chinese twin girl, aged 18 years, with the presence of a vagina and breasts but no uterus and ovaries and chromosomal karyotype analysis showing 46, XY, who was diagnosed with complete androgen insensitivity syndrome. The patient underwent bilateral gonadectomy and hormone replacement therapy, and pathological diagnosis showed immature testicular tissue development. CONCLUSION: In addition to rebuilding the external genitalia and preventing the emergence of gonadal tumors, continuing hormone replacement therapy after surgery is critical for the treatment of complete androgen insensitivity syndrome, and patients' psychological difficulties should be addressed.
Yearbook of pediatric endocrinology · 2022 · 0 citations
Metabolic effects of estradiol versus testosterone in complete androgen insensitivity syndrome
AbstractBrief Summary: In this multicentre, randomized, double-dummy, double-blind crossover trial the authors investigated differences in metabolic parameters between the individuals with complete androgen insensitivity syndrome (CAIS) receiving testosterone versus estradiol replacement therapy. This is the first study investigating these different treatment options in CAIS. It finds no major differences in metabolic and safety parameters between the treatments.
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.
