DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for ureterolithiasis — screening already-approved drugs against its 34-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUreterolithiasis maps to a 34-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 ureterolithiasis 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
protein kinase N1 (PKN1) — PKN1 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 drndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4OTH · 1.8 Å · ligand BISINDOLYLMALEIMIDE IX (DRN). Experimental structure, not a prediction.
What the evidence adds up to
A 2003 retrospective review of 176 patients undergoing 182 ureteroscopic procedures found that overall stone extraction rates actually declined from 94.4% in 1992 to 88.5% in 1998 (p=0.05), despite increased use of flexible ureteroscopy (11.5% to 29.4%) and more frequent attempts at proximal stones. Distal stone extraction was 97.2% in 1992 versus 95.1% in 1998 (p=0.43), and proximal extraction was 76.5% versus 71.9% (p=0.73); complication rates were similar (12% vs 10.2%, p=0.76). The authors concluded that technological advances permitted more aggressive instrumentation but did not translate into better efficacy of calculus treatment, though outpatient care rose from 50% to 76.1%.
A 2007 study of a new 270° semiflexible ureteroscope (Flex-X) compared it with an established device in vitro, ex vivo, and in 32 patients with lower pole stones. The new scope achieved deflection angles up to 270 degrees with an empty working channel, and thin probes did not inhibit deflection; durability was high with only minimal loss of deflection and three broken optical fibres after 100 ex vivo procedures. In clinical use, a stone-free rate of 100% was achieved after 4 weeks, though in three patients the basket opening mechanism failed at maximum deflection due to high friction. A 2009 review of 107 patients undergoing flexible or semi-rigid ureteroscopy with Ho:YAG laser lithotripsy found initial stone-free rates of 91%, 97%, and 94% in normal, overweight, and obese individuals respectively, with no significant differences (p=0.26 and 0.50); for renal and proximal ureteral stones the rate was 94% in both overweight and obese groups, and 100% for distal stones in both groups.
A 2015 prospective randomised study of 138 patients with proximal ureteral calculi (stone size 10–15 mm) after ureteroscopic Ho:YAG laser lithotripsy compared a control group, a tamsulosin group, and a Chinese herbal formula group (Removing Stasis and Reducing Heat Formula) over 4 weeks. Of 131 patients available for follow-up, the stone-free rate at 2 weeks was significantly higher in the tamsulosin (95.56%) and herbal formula (97.62%) groups than in the control (79.55%, all P<0.05). Ureteral colic rate and mean fragment expulsion time were reduced in the tamsulosin (4.44% and 7.86±4.99 days) and herbal formula (2.43% and 6.76±4.37 days) groups compared with control (22.73% and 11.54±9.89 days, all P<0.05). The herbal formula group also differed significantly from control in total International Prostate Symptom Score, irritative and obstructive subscores, and quality of life score at stent removal.
A 2022 case report describes a 25-year-old male with a left-sided ureteric calculus of 5.6 mm at the uretero-vesicular junction with ipsilateral hydro-uretero nephrosis, treated successfully with Lycopodium clavam in LM potency over 50 days. A 1922 paper discusses intravesical management of ureteral obstructions, noting that ureteral calculus was considered an ailment demanding surgical intervention scarcely a decade earlier, and credits early workers for advancing diagnosis and treatment through dilation and medicinal treatment. A 2005 review and a 2012 review cover molecular and genetic factors in urolithiasis and ureter development respectively, but provide no clinical outcome data. Missing from the evidence is any randomised comparison of the herbal formula against tamsulosin alone, long-term follow-up beyond 4 weeks for stone recurrence, and prospective data on whether newer endoscopes improve stone-free rates in proximal stones where the 2003 data showed no gain; no trial addresses cost-effectiveness or patient stratification by stone composition or ureteral anatomy.
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 · 2003 · 116 citations
Ureteroscopy: Effect of Technology and Technique on Clinical Practice
AbstractPURPOSE: Technical advances in ureteroscopy allow for more aggressive management of upper tract pathology. We evaluate to what extent clinical practice and treatment efficacy have been impacted by improvements in technology and technique. MATERIALS AND METHODS: In 1998, 176 consecutive patients underwent 182 ureteroscopic procedures at our institution. Retrospective chart review was performed. Factors such as clinical indication, pathology location, type of ureteroscope, procedure duration, procedure success, complication rate and length of stay were evaluated. Data from the 1998 cohort were compared to those obtained from a cohort of patients from 1992. Statistical analysis was performed using chi-square test. RESULTS: Overall stone extraction rate was 94.4% (1992) vs 88.5% (1998) (p = 0.05). Proximal stones were treated in 13.5% (1998) vs 28.3% (1998) of cases. Distal stone extraction rate was 97.2% (1992) vs 95.1% (1998) (p = 0.43) and proximal stone extraction rate was 76.5% (1992) vs 71.9% (1998) (p = 0.73). Diagnostic inspection success rate was 98.3% (1992) vs 98.3% (1998). Use of flexible ureteroscopy was 11.5% (1992) vs 29.4% (1998). Complication rate was 12% (1992) vs 10.2% (1998) (p = 0.76). Of the cases 76.1% were outpatient in 1998 vs only 50% in 1992. CONCLUSIONS: Recent advances in ureteroscopic technology permit more aggressive instrumentation of the upper tract as reflected in higher use of flexible ureteroscopy and more frequent attempts to manage proximal ureteral calculi. These advances have not translated into better efficacy of calculus treatment. Furthermore, our data reflect a nationwide trend toward outpatient treatment.
Journal of the American Society of Nephrology · 2012 · 49 citations · open access
Cell Biology of Ureter Development
AbstractThe mammalian ureter contains two main cell types: a multilayered water-tight epithelium called the urothelium, surrounded by smooth muscle layers that, by generating proximal to distal peristaltic waves, pump urine from the renal pelvis toward the urinary bladder. Here, we review the cellular mechanisms involved in the development of these tissues, and the molecules that control the process. We consider the relevance of these biologic findings for understanding the pathogenesis of human ureter malformations.
Cellular and Molecular Gateways to Urolithiasis: A New Insight
AbstractUrolithiasis is a relevant clinical problem in everyday practice with a subsequent burden for the health system. Urolithiasis is classically explained as the derangement in the process of biomineralization involving the equilibrium between promoters and inhibitors of crystallization: a deficit of one or several inhibitors or an excess of one or several promoters plays a pivotal role in the stone formation. The revolutionary introduction of the molecular biology in medicine has given a new insight in urolithiasis too. Genetic factors have also been postulated to play an important role. A review of the current knowledge on urolithiasis based upon a molecular and genetic approach is reported.
Ureteroscopy for Stone Treatment Using New 270° Semiflexible Endoscope: <i>In Vitro, Ex Vivo</i> , and Clinical Application
AbstractBACKGROUND AND PURPOSE: The use of flexible ureteroscopy for diagnosis and management of upper urinary tract diseases is limited both by loss of maximum active deflection through the inserted working probes and a high frequency of damage with consequent costs. A newly developed ureteroscope (Flex-X, Karl Storz) with a maximized angle of deflection was introduced to overcome these problems. The aim of our study was to compare this new ureteroscope with an established device in vitro, ex vivo, and in a clinical approach. MATERIALS AND METHODS: Angles of maximum active deflection and maximum irrigation flow were measured for both scopes in vitro with an empty working channel and after introduction of different lithotripsy and stone extraction probes. In addition, the loss of maximum active deflection and broken optical fibers of the scopes were assessed after 100 flexible ureteroscopies in an ex-vivo pig cadaver model. The clinical performance of both ureteroscopes was evaluated in 32 patients for management of lower pole stones. RESULTS: The new ureteroscope displays highly improved deflection compared with the standard scope; deflection angles as much as 270 degrees with an empty working channel were achieved. Thin probes did not inhibit maximum deflection. Durability in ex vivotrials was high. Only minimal loss of maximum deflection and three broken optical fibers were observed. In clinical usage, a stone-free rate of 100% was achieved after 4 weeks. In three patients, the opening mechanism of a basket did not work with maximum deflection because of high friction. CONCLUSION: The new ureterorenoscope facilitates retrograde stone management and might diminish repair intervals. Further development of comparable devices will support flexible ureterorenoscopy as a standard stone management procedure.
International braz j urol · 2009 · 24 citations · open access
Impact of obesity on ureteroscopic laser lithotripsy of urinary tract calculi
AbstractPURPOSE: The treatment of urinary tract stones in obese patients may differ from the treatment of non-obese patients and their success rate varies. Our objective was to compare ureteroscopic treatment outcomes of ureteral and renal stones, stratified for stone size and location, between overweight, obese and non-obese patients. MATERIALS AND METHODS: Charts were reviewed for 500 consecutive patients presenting at our institution for renal and ureteral stones. A total of 107 patients underwent flexible or semi-rigid ureteroscopy with Ho:YAG laser lithotripsy and met criteria for review and analysis. RESULTS: Overall, initial stone-free rates were 91%, 97%, and 94% in normal, overweight and obese individuals respectively. When compared to non-obese patients, there were no significant differences (p value = 0.26; 0.50). For renal and proximal ureteral stones, the stone-free rate in overweight and obese individuals was 94% in both groups; and a stone-free rate of 100% was found for distal stones, also in both groups. CONCLUSIONS: Ureteroscopic treatment of stones in obese and overweight patients is an acceptable treatment modality, with success rates similar to non-obese patients.
INTRAVESICAL MANAGEMENT OF OBSTRUCTIONS IN THE URETER
AbstractIt is only recently that the clinician has been devoting serious attention to the ureter. We are now coming to appreciate the fact that not a few cases of intraabdominal pain are directly traceable to abnormalities in this structure. Scarcely a decade ago ureteral calculus was considered an ailment which demanded surgical intervention. The possibility of there being a definite pathologic entity which might be termed ureteral stricture was but yesterday seriously questioned. Even today hardly a textbook on urology contains within its covers the term ureteritis. Thanks to the courage of such workers as Kelly, Buerger, Bransford Lewis, Hunner, Crowell and many others too numerous to mention, our methods of diagnosis and treatment of ureteral obstructions have reached a plane of scientific exactness which are a source of great satisfaction and pride to all American urologists. The fact that, by dilation and medicinal treatment to the ureter through the
International Journal of Homoeopathic Sciences · 2022 · 0 citations · open access
A case report of left sided ureteric calculus cured by lycopodium clavam in lm potency
AbstractUretric calculus or stone in ureter is one of an acute abdominal condition, if it not managed properly it may transferred to fatal condition. Calculus of ureter mainly originates from kidney & passes down to ureter. While passing down it may stuck in to the narrowest constrictions in Ureteric lumens, leads to obstruction of ureter results in Uretric colic & hydonephrosis. A case of 25yrs old male patient with of Left sided ureteric calculus of 5.6mm at Uretero-vesicular junction with ipsilateral hydro-uretero nephrosis has been successfully treated by Lycopodium as a constitutional medicine at LM potency for a duration of 50 days.
Role of Removing Stasis and Reducing Heat Formula in Clearance of Proximal Ureteral Calculi after Ureteroscopic Ho:YAG Laser Lithotripsy: A Prospective Randomized Study
AbstractOBJECTIVE: To prospectively evaluate the efficacy of Removing Stasis and Reducing Heat Formula in accelerating calculus clearance and improving lower urinary tract symptoms of patients with proximal ureteral calculi after ureteroscopic Ho:YAG laser lithotripsy. METHODS: A total of 138 patients with proximal ureteral calculi underwent ureteroscopic Ho:YAG laser lithotripsy by a single endocrinologist. Stone size varied from 10 to 15 mm. After operation, the patients were randomly divided into three groups: the control group (group A), tamsulosin group (group B), and Removing Stasis and Reducing Heat Formula group (group C). The treatment lasted for 4 weeks or until stone clearance. The primary and secondary outcomes of the three groups at follow-up were assessed. RESULTS: Of the 131 patients available for follow-up, 44 cases were in the group A, 45 in the group B, and 42 in the group C, respectively. The stone free rate at 2 weeks in the groups B and C were significantly higher than that in the group A (95.56%, 97.62% vs. 79.55%; all P<0.05). The ureteral colic rate and mean time of fragment expulsion were significantly reduced in the groups B (4.44% and 7.86±4.99 days) and C (2.43% and 6.76±4.37 days) compared with the group A (22.73% and 11.54±9.89 days, all P<0.05). On the day of double-J ureteric stent removal, the group C differed significantly from the group A in the total International Prostate Symptom Score, irritative subscore, obstructive subscore, and quality of life score (all P<0.05). CONCLUSION: Removing Stasis and Reducing Heat Formula in the medical expulsive therapy might be an effective modality for patients with calculus in the proximal uretera after ureteroscopic Ho:YAG laser lithotripsy.
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.
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