DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 46,XY sex reversal 4 — 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 module46,XY sex reversal 4 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 46,xy sex reversal 4 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
doublesex and mab-3 related transcription factor 1 (DMRT1) — DMRT1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4YJ0 · 3.814 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Three novel mutations were identified in three of six Chinese women with 46,XY sex reversal: two heterozygous point mutations in SRY and one heterozygous microdeletion in NR5A1. The women were aged 15 to 23 and presented with poor sexual development and primary amenorrhea. The study did not report any treatment or clinical outcome beyond the genetic findings.
A 2024 report identified a novel pathogenic variant in DHX37, c.2012G > C (p.Arg671Thr), in a single patient with 46,XY disorders of sex development. In vitro assays showed the variant significantly reduced protein expression levels but did not alter intracellular localisation. The authors note that 21 variants in DHX37 have now been reported in 58 cases of 46,XY DSD. No clinical outcome data for the patient were provided.
A 1983 paper describes ten cases of sex therapy that ended in treatment failure. The couples initially showed symptom reversal after incorporating psychodynamic techniques into conventional sex therapy, but this reversal triggered a recycling sequence of relapses. The authors call this pattern "therapeutic gridlock" and "interminable" sex therapy. The paper is not about 46,XY sex reversal and does not involve any of the genes discussed in the other abstracts.
No controlled trials, no survival data, no response rates, and no drug treatments appear in any of these abstracts. What is missing for 46,XY sex reversal 4 specifically is any clinical trial testing a therapy, any patient stratification beyond genetic diagnosis, and any funding for treatment studies rather than case reports.
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 Maternal-Fetal & Neonatal Medicine · 2011 · 5 citations
Mutation analysis of the<i>SRY, NR5A1</i>, and<i>DHH</i>genes in six Chinese 46,XY women
AbstractOBJECTIVE: To determine the genetic cause of 46,XY sex reversal in six Chinese women. METHODS: G-banded karyotyping and mutation analysis of the SRY, NR5A1, and DHH genes using direct sequencing were performed in six Chinese women aged from 15- to 23-year old with poor sexual development and primary amenorrhea. Clinical, endocrinologic, and ultrasonographic evaluation was reported. RESULTS: Three novel mutations, two heterozygous point mutations in SRY, and one heterozygous microdeletion in NR5A1 were found to be causative in three of the patients. CONCLUSION: This helps pathogenic study and provides new information for genetic counseling of 46,XY sex reversals.
Molecular Genetics & Genomic Medicine · 2024 · 3 citations · open access
Identification and functional analysis of a rare variant of gene <scp><i>DHX37</i></scp> in a patient with 46,<scp>XY</scp> disorders of sex development
AbstractBACKGROUND: 46,XY sex reversal 11 (SRXY11) [OMIM#273250] is characterized by genital ambiguity that may range from mild male genital defects to gonadal sex reversal in severe cases. DHX37 is an RNA helicase that has recently been reported as a cause of SRXY11. So far, a total of 21 variants in DHX37 have been reported in 58 cases with 46,XY disorders of sex development (DSD). METHODS: Whole exome sequencing (WES) was conducted to screen for variations in patients with 46,XY DSD. The subcellular localization of mutant DHX37 proteins was detected by immunofluorescence. And the levels of mutant DHX37 proteins were detected via Western blotting. RESULTS: A novel pathogenic variant of DHX37 was identified in a patient with 46,XY DSD c.2012G > C (p.Arg671Thr). Bioinformatics analysis showed that the protein function of the variant was impaired. Compared with the structure of the wild-type DHX37 protein, the number of hydrogen bonds and interacting amino acids of the variant protein were changed to varying degrees. In vitro assays revealed that the variant had no significant effect on the intracellular localization of the protein but significantly reduced the expression level of the protein. CONCLUSIONS: Our finding further expands the spectrum of the DHX37 variant and could assist in the molecular diagnosis of 46,XY DSD patients.
Journal of Marital and Family Therapy · 1983 · 2 citations
INTERMINABLE SEX THERAPY: A REPORT ON TEN CASES OF THERAPEUTIC GRIDLOCK
AbstractThis paper reports on ten cases in which treatment began with conventional sex therapy and was later modified by incorporating techniques of psychodynamic couple therapy. While the modifications initially led to symptom reversal, the reversal of symptoms activated a recycling sequence of relapses and renewed symptom reversals, ultimately terminating in treatment failure. While the ten couples were heterogeneous in many respects, they did form a distinct clinical group. In common, they demonstrated a set of characteristics laced with hate, love and dependency, which interacted to create what the authors have called “therapeutic gridlock” and “interminable” sex therapy.
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.
