DeCure for Complete androgen insensitivity syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for complete androgen insensitivity syndrome — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleComplete androgen insensitivity syndrome maps to a 1-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 complete 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.
Loading structure…
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
In 24 patients with androgen insensitivity syndrome, 19 with the complete form and 5 with the partial form, sequencing of the androgen receptor gene identified 12 previously unreported mutations and 9 recurrent mutations. Three novel frameshift mutations — caused by a single nucleotide deletion, a single nucleotide insertion, or a 13‑base‑pair deletion — led to premature termination of the protein and were found only in patients with complete androgen insensitivity syndrome. A further premature stop codon in a complete‑form patient resulted from a previously reported nucleotide substitution in exon 5. A novel duplication of codon 788 was also found in a complete‑form patient. All other mutations were single base substitutions spread across exons 2 through 8 and were associated with either complete or partial forms. The authors concluded that apart from truncating mutations, a reliable genotype‑phenotype correlation could not be established, and that modifying factors must therefore be effective.
A separate case report described a 46,XY female with normal external genitalia who carried a novel de novo insertion, c.1669_1670insC, in the androgen receptor gene. The authors stated that this insertion caused androgen insensitivity syndrome and that the report should be useful for genetic counselling. No other patients or quantitative outcomes were reported in that study.
A 2024 case report described an adult patient with complete androgen insensitivity syndrome diagnosed belatedly. Surgical treatment was deemed necessary because of an elevated risk of gonadal malignancy. The report did not provide any numerical data on malignancy incidence, survival, or response to any intervention.
No drug treatment was mentioned in any of these abstracts. What remains missing is any clinical trial testing a pharmacological intervention for complete androgen insensitivity syndrome, any systematic data on the natural history of gonadal malignancy risk in untreated patients, and any evidence that patient stratification by mutation type could guide management beyond the clear truncating‑mutation cases.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Hormone Research in Paediatrics · 2005 · 46 citations
Novel and Recurrent Mutations in Patients with Androgen Insensitivity Syndromes
AbstractBACKGROUND/AIMS: Androgen insensitivity syndrome (AIS) caused by mutations within the androgen receptor gene represents a variety of phenotypes from females with 46,XY karyotype over individuals with ambiguous genitalia to infertile males. METHODS: We studied 24 patients with AIS by sequencing androgen receptor gene. 19 of the investigated patients were affected by complete androgen insensitivity syndrome (CAIS) and 5 suffered from partial androgen insensitivity syndrome (PAIS). RESULTS: So far we have detected 12 unreported mutations as well as 9 recurrent mutations (3 recurrent mutations were detected twice) in exons 2-8 of the androgen receptor gene. Three of the novel mutations cause a frameshift with subsequent premature termination and were found in patients with CAIS. These frameshifts were induced by single nucleotide deletion or insertion, or in one case by a 13-bp deletion, respectively. Another premature stop codon found in a CAIS patient results from an already reported nucleotide substitution in exon 5. Furthermore, in a CAIS patient we found a novel duplication of codon 788. All other mutations caused single base substitutions spread through exons 2-8 and were associated with CAIS or PAIS. CONCLUSIONS: We report a broad spectrum of different mutations within the AR gene leading to various manifestations of AIS. Apart from truncating mutations, a reliable genotype/phenotype correlation cannot be established. Therefore, modifying factors must be effective.
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.
Rare Case of Complete Androgen Insensitivity Syndrome
AbstractAndrogen insensitivity syndrome is a rare X-linked recessive condition in which patients present a female phenotype. After complete androgen insensitivity syndrome (CAIS) diagnosis, the timing of gonadectomy should be evaluated, considering the risks and benefits of this procedure. This paper reports an uncommon case of complete androgen insensitivity syndrome diagnosed belatedly in an adult patient. Surgical treatment was deemed necessary due to the elevated risk of gonadal malignancy.
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.
