DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for infertility — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInfertility maps to a 35-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
approvedDanazolApproved drug
Structures already discussed alongside infertility in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Sex Hormone-binding globulin mutant E176K — Danazol has a real, experimentally solved structure in complex with this target (PDB 6ULB, 1.75 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet qa1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ULB · 1.75 Å · ligand Danazol (QA1). Experimental structure, not a prediction.
What the evidence adds up to
Infertility affects 8–12% of reproductive-aged couples worldwide, with a male factor identified in about half of cases. In roughly 30% of those male cases the cause remains unknown, a situation termed idiopathic male infertility. A 2018 review of medical treatments for idiopathic male infertility states that the compounds with the strongest evidence of efficacy and the most used in clinical practice are follicle-stimulating hormone (FSH) and estrogen receptor selective modulators (SERMs). Non-hormonal treatments include antioxidants and prokinetic agents, but the review notes these are supported by variable degrees of evidence. The authors emphasise that therapy must be personalised because patients differ in clinical features, and that new targeted therapies depend on investigating the underlying pathophysiological mechanisms.
For unexplained infertility in couples where standard investigations reveal no abnormality, a 1999 review reports that danazol and bromocriptine show no benefit. Clomiphene citrate can double the spontaneous pregnancy rate. Induction of ovulation with human menopausal gonadotrophin (hMG) yields an overall pregnancy rate between 2 and 26% per cycle, which appears lower than the 25–30% per cycle reported for in vitro fertilisation (IVF) or gamete intrafallopian transfer (GIFT) in similar patients. The review proposes a rational treatment plan of up to four cycles of clomiphene citrate with or without intrauterine insemination (IUI), followed by superovulation with hMG and IUI for three cycles, and then assisted reproductive techniques if unsuccessful.
A 2024 editorial on the search for causes of infertility summarises recent genetic studies. In cervical cancer, specific single nucleotide polymorphisms (SNPs) in microRNA genes (rs107822 of miR-219a and rs2292832 of miR-149) were associated with cancer risk, potentially through the PI3K/Akt signalling pathway. In ovarian endometriosis, WTAP gene polymorphisms (rs1853259 and rs7766006) were linked to altered susceptibility in Chinese women. A novel CLPP gene variant was found to affect mitochondrial function and trigger granulosa cell apoptosis, potentially contributing to premature ovarian insufficiency. In male infertility, recessive loss-of-function mutations in the TEX15 gene were associated with spermatogenic failure (oligozoospermia, nonobstructive azoospermia) in humans and in a knockout mouse model. A Mendelian randomisation study found a potential link between genetically predicted chronotype and testosterone levels, but no significant association between other sleep traits and male fertility.
What remains missing is the translation of these genetic associations into validated therapies. The 2018 review calls for investigation of pathophysiological mechanisms to develop targeted treatments, but such drugs are not yet available. The 1999 review’s treatment plan relies on empirical ovarian stimulation rather than mechanism-based drugs. The 2024 editorial identifies candidate genetic variants and pathways but does not report any clinical trial testing a drug based on them. No randomised controlled trial has yet demonstrated that targeting any of these genetic variants improves pregnancy rates. Funding for large, stratified trials and for drug development based on the newly identified mechanisms is still lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Expert Opinion on Pharmacotherapy · 2018 · 76 citations
Current and emerging medical therapeutic agents for idiopathic male infertility
AbstractINTRODUCTION: Infertility is one of the great challenges of modern healthcare. It afflicts about 8-12% of reproductive-aged couples worldwide, but the prevalence is even higher in industrialized countries. In 50% of cases, a male factor of infertility underlies the problem, but in about 30% of these cases the etiology of male infertility remains unknown. This eventuality, called idiopathic infertility, requires empirical medical therapy and/or assisted reproductive techniques. AREAS COVERED: This article reviews the literature about the medical treatments available for idiopathic male infertility. These treatments can be divided into two main categories: hormonal therapies and non-hormonal therapies. The compounds with the strongest evidence of efficacy and the most used in clinical practice for the treatment of idiopathic male infertility are follicle-stimulating hormone (FSH) and estrogen receptor selective modulators (SERMs). Non-hormonal treatments include a series of compounds with antioxidant and prokinetic properties, supported by variable degrees of evidence of clinical efficacy. EXPERT OPINION: Patients with idiopathic infertility have peculiar clinical features that differentiate them from each other. Therapy must, therefore, be personalized to each patient. Furthermore, scientific research must investigate the pathophysiological mechanisms that underlie infertility; only in this way, new targeted therapies can be developed.
AbstractUNLABELLED: Unexplained infertility is a diagnosis made by exclusion after all of the standard investigations have revealed no abnormality (1). The range of the prevalence is from 6 to 60 percent (23), depending on the diagnostic criteria. This article reviews the literature in the management of unexplained infertility; published data suggest no benefit of danazol or bromocriptine. The empirical use of clomiphene citrate suggests that ovarian stimulation using clomiphene citrate can double the spontaneous pregnancy rate (52, 58, 59). Induction of ovulation with human menopausal gonadotrophin (hMG) yields an overall pregnancy rate between 2 and 26 percent per cycle (68, 74). These results seem to be lower than those reported for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) procedures in similar patients (25-30 percent (92, 95)). Based on the literature, a rational treatment plan for treating infertility in couples with unexplained infertility includes up to four cycles of clomiphene citrate with or without intrauterine insemination (IUI). Superovulation with hMG and IUI or stimulated intrauterine insemination (SIUI) is the next step for three-cycle treatments and if unsuccessful, one of the variants of assisted reproductive techniques (ART) should be considered. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will understand the appropriate tests and work up for unexplained infertility, the various treatment options for the unexplained infertility couple including which drugs are effective and not effective, and to be able to outline an appropriate treatment plan for such patients.
International Journal of Infertility & Fetal Medicine · 2017 · 2 citations
Efficacy of Cabergoline in the Prevention of Ovarian Hyperstimulation Syndrome: A Randomized, Double-blind and Placebo-controlled Trial
AbstractABSTRACT Introduction Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication that arises due to assisted reproductive technologies (ARTs) during infertility treatment. Recently, the use of selective dopamine receptor agonists on D2 receptors (e.g., cabergoline) has been suggested in the prevention of OHSS. The aim of this study was to evaluate the effect of cabergoline in the prevention of OHSS in high-risk patients undergoing ART. Materials and methods This was a randomized, double-blind, parallel group (cabergoline group and placebo) study. A total of 110 women undergoing in vitro fertilization (IVF)–intracytoplasmic sperm injection procedure using a long agonist protocol with high risk for OHSS were recruited for the study on the day of final trigger. All the patients were followed up every 48 hours for 10 days from the day of the final trigger and clinically assessed with ultrasound and blood tests. The size of ovaries and fluid collection in the pouch of Douglas (POD) was measured with ultrasound. A sample size of 92 subjects was calculated for the study to be powered at 80%. Assuming a drop-out rate of 10%, 110 subjects were enrolled for the study. Results There was no significant difference observed in the size of right and left ovary, POD fluid volume, total leukocyte count (TLC), and serum estradiol level (E2 level) between both the groups from day 0 to day 8, except packed cell volume. No significant difference was observed in the incidence rate of moderate OHSS between both groups (p = 0.728). The differences in clinical pregnancy rate, implantation rate, and live birth rate were also insignificant. Conclusion Cabergoline does not reduce the incidence of moderate OHSS when compared with placebo. Large, well-designed studies are needed to evaluate the effectiveness of cabergoline when used for the prevention of OHSS. How to cite this article Singh S, Singh S, Raman AK, Ramakrishnan S, Ashraf CM. Efficacy of Cabergoline in the Prevention of Ovarian Hyperstimulation Syndrome: A Randomized, Double-blind and Placebo-controlled Trial. Int J Infertil Fetal Med 2017;8(2):54-60
Frontiers in Genetics · 2024 · 0 citations · open access
Editorial: Searching for causes of infertility: from pathophysiologic mechanisms to therapeutic strategies
AbstractReproductive disorders are global health problems affecting millions of people worldwide. In humans, infertility is indeed a very serious disease that disturbs also mental health. In animals, it is not such a big problem, unless it involves, i.e., extinct species or precious specimens for the environment, farming, forestry, etc. In both humans and animals, it reflects abnormalities at many levels of the very complicated fertilization process. The search for the causes of the lack of offspring focuses primarily on the gametes themselvestheir fusion is the most important step in the fertilization process. The health of gametes depends on so many factors that it seems improbable that we reproduce.The discovery of new pathophysiological mechanisms affecting fertilization is a continuous process forced by the progress of methods. The innovative techniques used, e.g., advanced genomic analysis and functional experiments, provide robust evidence and insights into the genetic basis of reproductive health. Animal models greatly help to study of the fertilization process mechanisms.The investigation of genetic factors is currently the most promising type of biological research. Here, we recommend a collection of interesting publications on reproductive disorders, cervical cancer and male infertility. We hope that cognition of specific genetic variants and an understanding of the mechanisms involved in reproduction will refine the choice of therapies and contribute to global improvements in human and animal reproductive health.Three publications in this collection deal with the most serious dysfunctions of the female reproductive tract related to endometriosis, premature expiration of ovarian function, and cervical cancer. Studies of genetic variants indicate new polymorphisms that are candidates as potential biomarkers and could become new therapeutic targets. The publication by Chen et al. [Chen K, et al. 2022] concerns genetic polymorphisms in the world's most common cervical cancer in women. The authors investigated the association between specific genetic variations (SNPs) in microRNA genes involved in the PI3K/Akt signaling pathway and susceptibility to cervical cancer. Numerous researchers have pointed out that these dysregulated microRNAs could play an important role in cervical cancer development [Hillyar et al., 2023;Shen et al., 2020]. Some of the stage-specific microRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cervical cancer [Causin et al., 2021]. Chen showed that rs107822 of miR-219a and rs2292832 of miR-149 were associated with cervical cancer risk, indicating a potential role of microRNAs in cervical cancer development. They predicted that miR-219a could target integrins (ITGA and ITGB) that participate in the activation of the PI3K/Akt signaling pathway. Thus, the function of these two SNPs in cervical cancer development should be investigated and verified in the future.In the paper of Wan et al. [Wan Z et al., 2023] the association between three WTAP (Wilms tumor 1-associated protein) gene polymorphisms and ovarian endometriosis risk in Chinese women was addressed. Results indicated that specific WTAP variants may increase susceptibility to ovarian endometriosis among Chinese women. They found that the rs1853259 G variant genotypes significantly increased, whereas the rs7766006 T variant decreased the association with ovarian endometriosis risk and were correlated with the WTAP expression level.Premature ovarian insufficiency is characterized by early loss of ovarian function before the age of 40 years. This disease has genetic basis. The relationship between novel CLPP (caseinolytic mitochondrial matrix peptidase proteolytic subunit) gene variation and premature ovarian insufficiency was investigated by Yuan et al. [Yuan X et al. 2023]. Results suggested that novel CLPP gene variant affects mitochondrial function and triggers granulosa cell apoptosis, potentially contributing to the pathogenesis of premature ovarian insufficiency. Women's health is important not only for procreation but also for the health of the offspring [Suszyńska-Zajczyk J et al., 2024]. Suszynska-Zajczyk et al. investigated the effects of maternal hyperhomocysteinemia induced by a high-methionine diet on the health of their offspring. Elevated homocysteine levels, are a known risk factor for cardiovascular, renal, and neurological diseases as well as pregnancy complications. Results suggested sex-dependent effects on cognition, muscle strength, and breeding outcomes in offspring. A high-metionine diet impairs memory and cognition in female juveniles and weakens muscle strength in male pups. These effects may stem from abnormal placental function affecting early neurogenesis, dysregulation of autophagy-related pathways in the cortex, or epigenetic mechanisms of gene regulation triggered by hyperhomocysteinemia during embryonic development.Men's health and the disturbances on the reproductive process are presented the next two publications. Qureshi S et al. [Qureshi S et al., 2023] used whole-exome and genome sequencing to identify novel, clinically significant variants in testis-expressed gene 15 (TEX15) in unrelated men with spermatogenic failure (oligozoospermia, nonobstructive azoospermia). The authors found that recessive loss-of-function TEX15 mutations are associated with spermatogenic failures (meiotic double-strand break repair) in humans and a knockout male mice model. Lu S et al. investigated the association of sleep traits with male fertility [Lu S et al., 2024], such as the relationship between sleep-related traits (chronotype, sleep duration, insomnia, snoring, dozing, daytime nap, oversleeping, and undersleeping), abnormal sperm or bioavailable testosterone levels using Mendelian randomization analysis. Results suggested a potential link between genetically predicted chronotype and testosterone levels, but no significant association was observed between other sleep traits and male fertility. The authors point out that the human biological clock may be important in reducing the risk of male infertility.A common topic among all listed studies is the investigation of genetic factors and their impact on various aspects of reproductive health and disease. Using advanced genomic techniques, these studies explored the role of genetic variations (single nucleotide polymorphisms (SNPs) or gene mutations) in conditions such as: cervical cancer, male fertility, spermatogenic failure, premature ovarian insufficiency, endometriosis, and hyperhomocysteinemia-induced deficits in offspring. They also highlighted the importance of understanding the genetic basis of reproductive disorders for improving diagnosis, prognosis, and potential therapeutic interventions. In summary, genetic factors play a significant role in the development and progression of various reproductive disorders, and studying these factors can provide valuable insights into their underlying mechanisms and potential clinical implications [Nagirnaja et al., 2022;Malcher et al., 2022;Turkyilmaz et al., 2022]. Despite focusing on different conditions, all studies investigated how genetic variations contribute to disease susceptibility or reproductive health outcomes. Each study contributes valuable insights to its respective field, highlighting the complex interplay among genetics, environmental factors, and disease susceptibility or reproductive health.
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.
