DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 46,XY sex reversal 6 — 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 6 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 6 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
mitogen-activated protein kinase kinase kinase 1 (MAP3K1) — MAP3K1 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 6WHB · 1.90032055102 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In the B6-Y(POS) mouse model of XY sex reversal, where mice with B6 autosomes and a wild-derived Y chromosome show complete sex reversal, a 1.62-Mb congenic region on chromosome 11 was found to confer 80% protection from sex reversal when one copy is present and complete protection when two copies are present. This region lies within the Sox9 promoter and promotes Sox9 expression, driving testis development. The protective region was maintained through 30 years of backcrossing because it promoted male sex determination and fertility despite the female-promoting B6-Y(POS) background. No drug was tested or mentioned in this study.
In six Chinese women aged 15 to 23 with 46,XY sex reversal, poor sexual development, and primary amenorrhea, mutation analysis of SRY, NR5A1, and DHH genes found three novel mutations: two heterozygous point mutations in SRY and one heterozygous microdeletion in NR5A1, which were causative in three of the six patients. No drug was tested or mentioned in this study.
A separate report on ten couples in sex therapy described a pattern where conventional sex therapy modified with psychodynamic couple techniques initially reversed symptoms, but this reversal activated a recycling sequence of relapses and renewed symptom reversals, ultimately ending in treatment failure. The authors called this "therapeutic gridlock" and "interminable" sex therapy. This paper does not concern 46,XY sex reversal 6 and no drug was tested.
What is still missing for 46,XY sex reversal 6 is any clinical trial of a drug, any identified drug candidate, any patient stratification beyond genetic mutation screening, and any funding directed toward pharmacological intervention. The mouse work identifies a regulatory region but not a druggable target, and the human mutation studies are diagnostic only.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Experimental and Therapeutic Medicine · 2014 · 22 citations · open access
46,XY female sex reversal syndrome with bilateral gonadoblastoma and dysgerminoma
AbstractSex reversal syndrome is a rare congenital condition of complete or disordered gonadal development leading to discordance between the genetic, gonadal and phenotypic sexes, including 46,XX and 46,XY. The gonadoblastoma on the Y-chromosome (GBY) region is associated with an increased risk of developing type II germ cell tumors/cancer. The present study reports a unique case of a phenotypically normal female (age 17 years), presenting with primary amenorrhea and later diagnosed with 46,XY female sex reversal syndrome. Following bilateral gonadectomy, bilateral gonadoblastoma and dysgerminoma were diagnosed. Thus, estrogen replacement therapy was administered periodically to promote the development of secondary sexual characteristics and menstruation, and to prevent osteoporosis. A four year follow-up showed no tumor recurrence and a regular menstrual cycle in this patient.
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.
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.
