DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spermatogenic failure 1 — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSpermatogenic failure 1 maps to a 4-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 spermatogenic failure 1 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 5 group A member 1 (NR5A1) — NR5A1 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4QJR · 2.4 Å · ligand (2S)-3-{[(R)-{[(1S,2S,3R,4S,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonooxy)cyclohexyl]oxy}(hydroxy)phosphoryl]oxy}propane
-1,2-diyl dihexadecanoate (PIZ). Experimental structure, not a prediction.
What the evidence adds up to
Medical therapy for primary spermatogenic failure remains largely ineffective. A 2011 review states that no treatments have consistently demonstrated efficacy, and it has not been possible to reliably identify patients likely to benefit. Treatment has been attempted with hormones and nutritional supplements (antioxidants), but idiopathic spermatogenic failure likely results from multiple discrete defects in sperm production that are as yet unidentified. The review notes that empiric medical therapy has been largely replaced by assisted reproductive techniques.
A 1988 study of 8879 consecutive vasectomies with uniform technique over 24 years found 97 failures of all types among a subgroup of 5331 men who returned for at least two postoperative semen tests. There were 32 (0.60%) early and overt failures, 61 (1.14%) technical failures involving persistence of small numbers of spermatozoa, and 4 (0.08%) late overt failures discovered as a result of pregnancy at least four years after two azoospermic test results. Four failures were due to missed vasa deferentia, and the remainder were attributed to recanalisation.
A 2022 review notes that male factor infertility contributes approximately 50% to the cause of infertility, and that semen quality is declining steadily worldwide. Assisted reproduction is the main treatment, but in severe male factor infertility, outcomes can end with recurrent implantation failure or recurrent pregnancy loss. Basic semen analysis still has limitations in explaining the cause of failure from the male factor part.
What is still missing is a better understanding of the discrete defects in sperm production, which would allow more effective treatment options and appropriate triage of patients. No trial has yet identified a reliably effective drug regimen for primary spermatogenic failure, and the field lacks patient stratification tools and funding for the basic research needed to identify the underlying defects.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Asian Journal of Andrology · 2011 · 57 citations · open access
Medical therapy for spermatogenic failure
AbstractMedical treatment of men with primary spermatogenic failure remains largely ineffective in contrast to those with secondary testicular failure. Treatment has been attempted with a multitude of agents ranging from hormones to nutritional supplements (antioxidants). While some studies have demonstrated benefit to some treatments, no treatments have consistently demonstrated efficacy nor has it been possible to reliably identify patients likely to benefit. Idiopathic spermatogenic failure likely results from multiple discrete defects in sperm production that are as yet unidentified. A better understanding of these defects will yield more effective treatment options and appropriate triage of patients to specific therapeutic regimens. This review focuses on the rationale and current evidence for hormonal and antioxidant therapy in medical treatment of male infertility, spermatogenic failure in particular. Although empiric medical therapy for spermatogenic failure has been largely replaced by assisted reproductive techniques, both treatment modalities could play a role, perhaps as combination therapy.
AbstractVasectomy techniques and failure rates vary among surgeons, and the criteria for failure are not often clearly defined. To help establish a yardstick for comparative purposes, a series of 8879 consecutive vasectomies performed with uniform technique over 24 years was reviewed. A subgroup of 5331 men who had returned for at least two postoperative semen tests—the<i>study</i>group—was used for follow-up analysis. Failures were defined as<i>early</i>or<i>late</i>and also were categorized as overt or<i>technical</i>according to the numbers, motility, or persistence of the remaining spermatozoa. There were 97 failures of all types, including 32 (0.60%) early and overt failures and 61 (1.14%) technical failures that involved the persistence of small numbers of spermatozoa, possibly of no significance. Four (0.08%) late overt failures were also seen; each of these was discovered as a result of a pregnancy, and each occurred at least four years after two azoospermic test results. Of the 97 failures, four were recognized as due to missed vasa deferentia, and the remainder were attributed to recanalization. Whether improved and reproducible failure rates can be consistently obtained by other techniques is not yet clear. (<i>JAMA</i>1988;259:3142-3144)
IntechOpen eBooks · 2022 · 1 citations · open access
Semen Analysis and Infertility
AbstractMale factor infertility contribute approximately at 50% for the cause of infertility. The steady declination of semen quality in men for all over the world might be from various factors such as life style changes, environmental toxicity, dietary contribution and social problems. Assisted reproduction is the main treatment of choice for male infertility; However, in severe male factor infertility, the treatment outcomes could end up with recurrent implantation failure or recurrent pregnancy loss. Basic semen analysis still has limitation to explain the cause of failure for the part of male factors. The purposes of developing new sperm evaluation methods are to improve the diagnostic tools for identifying the sperm defects, appraise of fertility potential and provide suitable treatment for an infertile couple, explain the cause of treatment failure from male factor part and measure the efficacy of male contraception.
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.
