DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypospadias — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypospadias maps to a 41-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 hypospadias 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 a 1996 study of 40 patients with isolated penile hypospadias, only one missense mutation in the androgen receptor gene was found, changing amino acid residue 546 from proline to serine in a case of distal shaft hypospadias. The other 39 patients showed no abnormalities. The authors concluded that androgen receptor gene mutations are a rare cause of hypospadias.
A 2007 microarray analysis compared gene expression in hypospadiac tissue to non-hypospadiac tissue, including tissue from a pair of fraternal twins where one had hypospadias and one did not. The study found significant differences in the expression of genes responsive to estrogen or interacting with the estrogen receptor, specifically CYR61, CTGF, ATF3 and GADD45beta. The authors interpreted this as support for the hypothesis that endocrine-active environmental compounds may contribute to hypospadias development.
For surgical management of complications from previous hypospadias surgery, a 2012 study of 50 men with a median follow-up of 89 months reported an initial success rate of 50% (25 of 50). After additional procedures in 18 of the 25 men whose initial treatment failed, the overall success rate rose to 76% (38 of 50). The most common presenting complication was urethral stricture (36 patients), followed by urethrocutaneous fistula (12), persistent hypospadias (7), hair in the urethra (6), and severe penile chordee (7). A 1996 technique paper described a double onlay preputial flap for primary proximal hypospadias repair in 18 patients aged 6 months to 9 years. Complications included one case each of urethrocutaneous fistula, persistent chordee, recessed meatus, and urethral diverticulum; all were corrected with minor procedures, and no urethral stricture occurred.
What remains missing are prospective trials that stratify patients by molecular subtype, funding for replication of the gene-expression findings in larger cohorts, and any randomised comparison of surgical techniques for primary or revision hypospadias repair.
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 · 1996 · 98 citations
Androgen Receptor Gene Mutations are Rarely Associated with Isolated Penile Hypospadias
AbstractPURPOSE: Hypospadias has no known single etiology but it has been linked to androgen insensitivity caused by mutations of the androgen receptor gene. The purpose of this study was to search for such mutations in cases of various degrees of isolated hypospadias to determine whether such an association exists and, if so, with any particular anatomical subgroup. MATERIALS AND METHODS: Isolated deoxyribonucleic acid from the penile tissue of 40 patients undergoing reconstructive surgery was screened for mutations of the coding regions of the androgen receptor gene using single strand conformational polymorphism analysis. In cases with abnormal single strand conformational polymorphism findings sequence analysis of the deoxyribonucleic acid was performed to define the mutation. RESULTS: A missense mutation of exon 2 of the androgen receptor gene was noted in 1 patient with isolated distal penile shaft hypospadias. Sequence analysis revealed that the mutation changed amino acid residue 546 from proline to serine. No abnormalities were detected in the other 39 patients. CONCLUSIONS: Isolated distal shaft hypospadias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.
Treatment of Adults with Complications from Previous Hypospadias Surgery
AbstractPURPOSE: Adults with complications from previous hypospadias surgery experience various problems, including urethral stricture, persistent hypospadias and urethrocutaneous fistula. Innate deficiencies of the corpus spongiosum and multiple failed operations makes further management challenging. MATERIALS AND METHODS: We reviewed our prospective urethroplasty database of men who presented with complications of previous hypospadias surgery. Patients were included in study if they had greater than 6 months of followup. Our surgical management was defined as an initial success if there were no urethral complications. The overall success rate included men with the same result after additional treatment. RESULTS: A total of 50 men had followup greater than 6 months (median 89) and were included in study. These 50 patients presented with urethral stricture (36), urethrocutaneous fistula (12), persistent hypospadias (7), hair in the urethra (6) and severe penile chordee (7). Patients underwent a total of 74 urethroplasties, including stage 1 urethroplasty in 19, a penile skin flap in 11, stage 2 urethroplasty in 11, urethrocutaneous fistula closure in 9, permanent perineal urethrostomy in 6, excision and primary anastomosis in 6, a 1-stage buccal mucosa onlay in 4, tubularized plate urethroplasty in 3, combined techniques in 3 and chordee correction in 1. In 25 men (50%) treatment was initially successfully. Of the 25 men in whom surgery failed 18 underwent additional procedures, including 13 who were ultimately treated successfully for an overall 76% success rate (38 of 50). CONCLUSIONS: Managing problems from previous hypospadias surgery is difficult with a high initial failure rate. Additional procedures are commonly needed.
Up-Regulation of Estrogen Responsive Genes in Hypospadias: Microarray Analysis
AbstractPURPOSE: An unexplained increase in the incidence of hypospadias has been reported, and yet to our knowledge the molecular events and their regulation leading to hypospadias remain unknown, although environmental compounds capable of endocrine activity are suspected. We screened on a global scale abnormalities in gene expression in human hypospadiac tissue compared to those in nonhypospadiac tissue. Additionally, microarray analysis of tissue from a pair of fraternal twins, including 1 with and 1 without hypospadias, served as a control for genetic variability. We hypothesized that gene expression would differ between hypospadiac vs nonhypospadiac tissue and fraternal twin data would show patterns similar to those of group data on hypospadiac and nonhypospadiac tissue. MATERIALS AND METHODS: Microarray analysis was performed on tissue from patients with and without hypospadias, and from a pair of fraternal twins, including 1 with and 1 without hypospadias. Analysis incorporated the expression of 22,000 genes. RESULTS: We found significant differences in gene expression, specifically with a group of genes, including CYR61, CTGF, ATF3 and GADD45beta, known to be responsive to estrogen or to interact with estrogen receptor. CONCLUSIONS: Our findings provide support for the hypothesis that endocrine active environmental compounds may contribute to the development of hypospadias. Additionally, regulation of these genes may have a role in formation of the urethra.
Double Onlay Preputial Flap for Proximal Hypospadias Repair
AbstractPURPOSE: We describe a new technique for primary repair of proximal hypospadias. The double onlay preputial flap combines the principles of onlay urethroplasty and the double face preputial flap, namely preservation of the urethral plate and use of a total preputial flap. MATERIALS AND METHODS: Common problems of classic onlay urethroplasty, including rotation and asymmetry of the penile shaft when the preputial flap is brought laterally around the shaft and the viability of the Byars flaps after dissecting the pedicle for the onlay flap, are avoided with this technique by passing the penis through a buttonhole incision in the pedicle of the total preputial flap. Onlay urethroplasty is performed using a secondary flap outlined from the total preputial flap. The remainder of the total preputial flap tissue is used to cover the ventral skin defect. RESULTS: Since June 1994, 18 patients 6 months to 9 years old (median age 10 months) underwent primary hypospadias repair with the double onlay preputial flap technique, representing 15% of all repairs performed. Complications included a urethrocutaneous fistula, persistent chordee, a recessed meatus and a urethral diverticulum in 1 patient each. In all cases complications were corrected surgically with minor procedures. No patient had urethral stricture. Functional and cosmetic results were satisfactory in all patients. CONCLUSIONS: This technique yields good functional and cosmetic results for proximal hypospadias repair.
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.
