DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 46,xx sex reversal 5 — 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,xx sex reversal 5 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,xx sex reversal 5 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
nuclear receptor subfamily 2 group F member 2 (NR2F2) — NR2F2 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 3CJW · 1.48 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
46,XY sex reversal 5 is a disorder of sex development. One study examined six Chinese women aged 15 to 23 with 46,XY sex reversal, primary amenorrhea, and poor sexual development. Direct sequencing of the SRY, NR5A1, and DHH genes found three novel mutations: two heterozygous point mutations in SRY and one heterozygous microdeletion in NR5A1. These were considered causative in three of the six patients. The other three patients had no identified mutation in those genes.
A mouse study used the C57BL/6J-Y(POS) model, in which mice with a B6 autosome background and a Y chromosome from Mus domesticus poschiavinus show complete sex reversal. A 1.62-megabase congenic region on chromosome 11, located within the Sox9 promoter, conferred 80% protection from sex reversal when one copy was present and complete protection when two copies were present. This region promoted Sox9 expression and drove testis development. The finding indicates that long-range enhancer regions can influence sex determination, but the work was done entirely in mice.
A separate study of reversal surgery in seven regretful male-to-female transsexuals, aged 33 to 53, who had undergone sex reassignment surgery elsewhere, reported that all seven were pleased with the aesthetic appearance of their genitalia and with their significantly improved psychological status after reversal phalloplasty. Follow-up ranged from 13 to 61 months. Complications were two fistulas and one stricture, all repaired by minor revision. This paper does not address 46,XY sex reversal 5.
What is still missing: no clinical trials exist for 46,XY sex reversal 5; no drug has been tested in any human patient with this condition; the genetic causes remain unknown in half the cases in the small human study; and the mouse findings have not been translated to human therapy. Funding for patient registries, functional studies of the non-coding region, and any attempt at pharmacological intervention is absent.
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 Sexual Medicine · 2016 · 74 citations · open access
Reversal Surgery in Regretful Male-to-Female Transsexuals After Sex Reassignment Surgery
AbstractINTRODUCTION: Sex reassignment surgery (SRS) has proved an effective intervention for patients with gender identity disorder. However, misdiagnosed patients sometimes regret their decision and request reversal surgery. This review is based on our experience with seven patients who regretted their decision to undergo male-to-female SRS. AIMS: To analyze retrospectively seven patients who underwent reversal surgery after regretting their decision to undergo male-to-female SRS elsewhere. METHODS: From November 2010 through November 2014, seven men 33 to 53 years old with previous male-to-female SRS underwent reversal phalloplasty. Preoperatively, they were examined by three independent psychiatrists. Surgery included three steps: removal of female genitalia with scrotoplasty and urethral lengthening, total phalloplasty with microvascular transfer of a musculocutaneous latissimus dorsi flap, and neophallus urethroplasty with penile prosthesis implantation. MAIN OUTCOME MEASURES: Self-reported esthetic and psychosexual status after reversion surgery and International Index of Erectile Function scores for sexual health after phalloplasty and penile prosthesis implantation. RESULTS: Follow-up was 13 to 61 months (mean = 31 months). Good postoperative results were achieved in all patients. In four patients, all surgical steps were completed; two patients are currently waiting for penile implants; and one patient decided against the penile prosthesis. Complications were related to urethral lengthening: two fistulas and one stricture were observed. All complications were repaired by minor revision. According to patients' self-reports, all patients were pleased with the esthetic appearance of their genitalia and with their significantly improved psychological status. CONCLUSION: Reversal surgery in regretful male-to-female transsexuals after SRS represents a complex, multistage procedure with satisfactory outcomes. Further insight into the characteristics of persons who regret their decision postoperatively would facilitate better future selection of applicants eligible for SRS.
Regulation of Sex Determination in Mice by a Non-coding Genomic Region
AbstractTo identify novel genomic regions that regulate sex determination, we utilized the powerful C57BL/6J-Y(POS) (B6-Y(POS)) model of XY sex reversal where mice with autosomes from the B6 strain and a Y chromosome from a wild-derived strain, Mus domesticus poschiavinus (Y(POS)), show complete sex reversal. In B6-Y(POS), the presence of a 55-Mb congenic region on chromosome 11 protects from sex reversal in a dose-dependent manner. Using mouse genetic backcross designs and high-density SNP arrays, we narrowed the congenic region to a 1.62-Mb genomic region on chromosome 11 that confers 80% protection from B6-Y(POS) sex reversal when one copy is present and complete protection when two copies are present. It was previously believed that the protective congenic region originated from the 129S1/SviMJ (129) strain. However, genomic analysis revealed that this region is not derived from 129 and most likely is derived from the semi-inbred strain POSA. We show that the small 1.62-Mb congenic region that protects against B6-Y(POS) sex reversal is located within the Sox9 promoter and promotes the expression of Sox9, thereby driving testis development within the B6-Y(POS) background. Through 30 years of backcrossing, this congenic region was maintained, as it promoted male sex determination and fertility despite the female-promoting B6-Y(POS) genetic background. Our findings demonstrate that long-range enhancer regions are critical to developmental processes and can be used to identify the complex interplay between genome variants, epigenetics, and developmental gene regulation.
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.
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.
