DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for bladder calculus — 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 moduleBladder calculus 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 bladder calculus 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
phosphodiesterase 4D (PDE4D) — PDE4D 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 difluoromethoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5WH6 · 1.6 Å · ligand 1-[4-(difluoromethoxy)-3-{[(3S)-oxolan-3-yl]oxy}phenyl]-3-methylbutan-1-one (AKJ). Experimental structure, not a prediction.
What the evidence adds up to
A 2022 case report describes a 29-year-old man with bladder exstrophy who twice suffered extrusion of a giant neobladder calculus through the anterior abdominal wall, the first episode treated in 2010 and a recurrence nine years later. The authors conclude that recurrence of large calculi should be seen as a paradigm for the importance of close follow-up in bladder exstrophy patients. No other abstract in this set addresses bladder calculus directly, and none reports any drug treatment for the condition.
The remaining abstracts concern bladder biology and other bladder disorders, not calculus. A 2012 pilot study in mice found that a synthetic derivative of antiproliferative factor (as-APF) significantly attenuated bladder epithelial repair after acetic acid-induced stripping, with mean epithelial area lower than controls on days 3–21 (p < 0.05) and reduced expression of uroplakin III and zonula occludens-1. The authors propose this as a model for interstitial cystitis/painful bladder syndrome, not a therapy. A 2015 expert review argues that urothelium, afferent nerves, and bladder blood vessels should be considered as a network of drug targets for overactive bladder, but provides no efficacy data. A 2009 microarray study of mouse bladder development identifies transcription factors, retinoic acid signalling, and midkine as involved in early differentiation, with midkine shown in organ culture to up-regulate smooth muscle differentiation markers; this is basic biology with no clinical application. A 2011 review describes in vitro differentiated human urothelial constructs for measuring barrier function, again without therapeutic claims. A 2004 review covers extracellular matrix roles in bladder development and proposes a hypothetical model. A 2019 think tank summary on bladder pain syndrome states that for all treatments, from behavioural to surgical, the numbers are limited and the evidence base is not strong.
A 2025 review of bladder preservation in urothelial carcinoma reports that intravesical chemotherapy with or without hyperthermia gave 52–65% progression-free survival at 2–3 years, drug-coated carrier systems gave complete remission in 50–83%, viral gene therapy 53% complete remission, and systemic checkpoint inhibitors 19–44% recurrence-free at one year, with bladder preservation rates of 49–100% and no worsening of overall survival. Only trimodal radiochemotherapy matched cystectomy long-term, with 74% freedom from metastases and 73% overall survival. This concerns cancer, not calculus, and no drug is named. For bladder calculus specifically, what is missing is any clinical trial, any animal model of stone formation, and any candidate drug; the abstracts provide no evidence for pharmacological prevention or dissolution of bladder stones.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMC Urology · 2012 · 35 citations · open access
A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study
AbstractBACKGROUND: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. There is no reliably effective therapy for IC/PBS, and no generally accepted animal model for the disorder in which potential therapies can be tested. Bladder epithelial cells from IC/PBS patients make a small glycopeptide antiproliferative factor or "APF" that inhibits proliferation, decreases tight junction protein expression, increases paracellular permeability, and induces changes in gene expression of bladder epithelial cells in vitro that mimic abnormalities in IC/PBS patient biopsy specimens in vivo. We therefore determined the ability of a synthetic APF derivative to inhibit bladder epithelial repair in mice. METHODS: The bladder epithelium of female CBA/J mice was stripped by transurethral infusion of 3% acetic acid, and mice were subsequently treated daily with one of three intravesical treatments [synthetic as-APF, inactive unglycosylated control peptide, or phosphate buffered saline carrier (PBS)] for 1-21 days. Fixed bladder sections were either stained with haematoxylin and eosin for determination of epithelial area by image analysis, or incubated with anti-uroplakin III (UPIII) or anti-zonula occludens type 1 (ZO-1) antibodies for immunofluorescence microscopy. Epithelial measurement data were analyzed by a two-way analysis of variance (ANOVA); post hoc comparisons of multiple groups were carried out using the Tukey-Kramer method. RESULTS: Bladder epithelial repair was significantly attenuated in as-APF-treated mice as compared to control mice on days 3-21 (p < 0.05); the mean epithelial/total area over all measured days was also significantly lower in as-APF-treated mice vs. mice in either control group by post hoc analysis (p < 0.0001 for both comparisons). UPIII and ZO-1 expression was also decreased in as-APF-treated mice as compared to mice in either control group by day 7 (UPIII) or day 14 (ZO-1). CONCLUSIONS: This model demonstrates in vivo effects of as-APF which abrogates bladder epithelial repair and expression of UPIII and ZO-1 in CBA/J mice following transurethral acetic acid infusion. As bladder epithelial thinning, decreased UPIII expression, and decreased ZO-1 expression are histopathologic features of IC/PBS patient biopsies, this model may be useful for studying the pathophysiology of IC/PBS and the effect of potential therapies.
Expert Opinion on Therapeutic Targets · 2015 · 21 citations
Therapeutic targets for overactive bladder other than smooth muscle
AbstractINTRODUCTION: For a long time, our concepts of regulation of urinary bladder function in health and disease as well as of the target structures of therapeutics have focused on detrusor smooth muscle cells. However, other structures including urothelium, afferent nerves and bladder blood vessels may also be important in pathophysiology and its treatment. AREAS COVERED: Based on a selective review of literature, we discuss the role of urothelium, afferent nerve fibers and bladder blood vessels in bladder pathophysiology and as targets for treatment. EXPERT OPINION: There is solid evidence now that multiple anatomical structures within the urinary bladder contribute to the regulation of its function and hence may be targets for established and emerging drugs. However, most previous studies have looked at the various target structures in isolation. In contrast, we propose that they should be seen as a network sensing and responding to alterations in the cellular environment or to xenobiotics. Studies are emerging in which the interaction of two of these structures is explored. Major advances in our understanding of bladder function are expected to result from studies integrating multiple such structures but these may be technically challenging and difficult to perform and interpret.
Unraveling the Genetic Landscape of Bladder Development in Mice
AbstractPURPOSE: To better understand the pathobiology of human congenital bladder abnormalities and disorders associated with dedifferentiation, such as bladder cancer, we must first unravel the biology of normal bladder development. Therefore, we performed microarray analysis focusing on determining the gene expression profile at the initiation of bladder development. MATERIALS AND METHODS: RNA was extracted from embryonic day 13 and 18 mouse bladders (anatomically equivalent to 7 and 13 weeks of human gestation) and gene expression was evaluated using microarrays. Alterations in select genes of biological interest were confirmed using real-time quantitative polymerase chain reaction and localization was determined by immunohistochemistry. RESULTS: The genetic profile in the initiating mouse bladder at embryonic day 13 was dominated by transcription factors, retinoic acid signaling genes, Eph/ephrin bidirectional signaling molecules and genes associated with regulating cell cycle and differentiation. Later in development at embryonic day 18 genes associated with smooth muscle, innervation and epithelial differentiation were up-regulated. In addition, we examined the functional role of midkine, which was highly expressed at embryonic day 13, using organ culture and to our knowledge we provide the first evidence that this growth factor up-regulates molecules associated with bladder smooth muscle differentiation. CONCLUSIONS: These data provide novel insights into molecules that orchestrate bladder development and highlight genes that may be involved in diseases associated with abnormal differentiation.
Neurourology and Urodynamics · 2019 · 12 citations
How can we improve the diagnosis and management of bladder pain syndrome? Part 2:ICI‐RS 2018
AbstractBACKGROUND: This paper summarises the discussion in a think tank at the International Consultation on Incontinence-Research Society (ICI-RS) 2018 about the treatment of bladder pain syndrome. AIMS: To review the treatments of bladder pain syndrome from behavioural treatments to surgical interventions. MATERIALS AND METHODS: Review the literature in the light of the think tank discussions. RESULTS: All guidelines recommend different levels of treatment starting with conservative behavioral treatments then introducing oral treatments followed by intravesical instillations. If these treatments fail then more invasive treatments such as botulinum toxin injections, neuromodulation, or surgery could be suggested. CONCLUSION: Unfortunately for all treatments, the numbers are limited and, therefore, the evidence base is not strong. Further suggestions for research are suggested.
Methods in molecular biology · 2011 · 11 citations
Permeability of Differentiated Human Urothelium In Vitro
AbstractThe urothelium plays a critical role in the bladder as a permeability barrier to urine. Whereas it was once considered a simple physical barrier, it is increasingly evident that urothelium has a regulatory role in maintaining the barrier both through self-repair and by mediating the transport of ions and small molecules across the transcellular and paracellular interfaces. The development of cell culture systems that replicate the morphological and differentiated features of human urothelium provides a versatile in vitro tool for exploring molecular and functional relationships in normal bladder physiology and for examining inherent changes in the urothelia of patients with dysfunctional bladder syndromes. In addition, it provides a useful platform to study the effect of pharmacological treatment on urothelial barrier function. In this review, we describe the development of differentiated urothelial cell constructs from in vitro-propagated normal human urothelial cells, and the application of methods to assess barrier function using transepithelial electrical resistance, water, urea, and dextran transport as objective and quantifiable parameters.
Cell Biology of Bladder Development and the Role of the Extracellular Matrix
AbstractThe bladder is unique. It is the most distensible organ in the body. If the normal pattern of development is disturbed, the bladder can become dysfunctional and poorly compliant. Renal outcome is intimately linked to bladder function and hence bladder development. In this review we describe our current knowledge of the molecular processes that govern bladder development, with particular emphasis on the role of the extracellular matrix. Finally, we suggest a hypothetical model for bladder development.
Deutsches Ärzteblatt international · 2025 · 1 citations
New bladder preservation strategies in urothelial carcinoma of the bladder.
AbstractBACKGROUND: 17 500 persons receive a new diagnosis of urothelial carcinoma of the bladder in Germany each year. Radical cystectomy is performed for muscle-invasive and for non-muscle-invasive, recurrent, high-risk tumors. Because this procedure carries a perioperative complication rate of 30-40% and impairs the patients' quality of life, options have been developed for intravesical and systemic bladder-preserving treatment. METHODS: This review is based on pertinent publications (up to July 2024) on bladder-preserving treatment methods that were retrieved by a selective search in the PubMed, Web of Science, and Cochrane Library databases. RESULTS: Multiple clinical phase II-III trials and observational studies are available. Carefully selected patients with recurrent, non-muscle-invasive, high-risk urothelial carcinoma received bladder-preserving treatment of the following kinds: intravesical chemotherapy with or without hyperthermia (52-65% progressionfree at 2-3 years); drug-coated carrier systems (complete remission, 50-83%); viral gene therapy (complete remission, 53%); systemic immunotherapy with checkpoint inhibitors (19-44% recurrence-free at 1 year). The rate of bladder preservation was 49-100%. No worsening of overall survival was observed. Treatments for muscle-invasive urothelial carcinoma included neoadjuvant chemotherapy followed by frequent follow-up, radical transurethral tumor resection, partial cystectomy, and trimodal radiochemotherapy (TMRT). Only TMRT yielded comparable long-term oncological results to those of cystectomy, with a 74% rate of freedom from metastases and an overall survival rate of 73%. Any type of bladder-preserving treatment requires meticulous long-term urooncological follow-up, with repeated cystoscopies, bladder biopsies, urine cytologies, and multiparametric bladder MRI. CONCLUSION: Bladder-preserving treatments should be considered part of the therapeutic armamentarium and should be critically discussed in an interdisciplinary setting.
IJU Case Reports · 2022 · 0 citations · open access
Recurrent giant neobladder calculus extrusion after bladder exstrophy repair
AbstractIntroduction: Patients with bladder exstrophy subjected to reconstructive surgeries are at risk of developing urinary calculus. Case presentation: We report the case of a 29-year-old male patient with bladder exstrophy who presented with a recurrent episode of extrusion of calculus through the neobladder and anterior abdominal wall. Calculus removal and reconstructive repair of the neobladder and abdominal wall were performed in 2010. Nine years following the procedure, the patient returned with new large neobladder calculus extrusion. Conclusion: Recurrence of large calculus should be seen as the new paradigm for the importance of close follow-up in bladder exstrophy patients.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, 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.
