DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intestinal obstruction — screening already-approved drugs against its 27-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIntestinal obstruction maps to a 27-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 intestinal obstruction 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
p21 (RAC1) activated kinase 6 (PAK6) — PAK6 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 ipadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4KS7 · 1.4 Å · ligand ISOPROPYL ALCOHOL (IPA). Experimental structure, not a prediction.
What the evidence adds up to
A 2014 rabbit study of experimental intestinal obstruction found that the condition disrupts intestinal homeostasis in a phased manner. Obstruction caused goblet cell damage and reduced cell number, along with decreased serum citrulline levels and claudin 1 gene expression, and a transient increase in ornithine decarboxylase activity. The wet/dry weight ratio and pH of the intestinal lumen were dramatically altered, and the ratio of Bacillus bifidus to enterobacteria reversed. The number and area of Peyer's patches first increased then sharply decreased, accompanied by a change in the CD4/CD8 T-cell ratio driven by an increase in CD3+ and CD8+ T cells and a decrease in CD4+ T cells. The number of lamina propria lymphocytes gradually decreased with prolonged obstruction.
A 2017 literature review describes the main etiological factors of intestinal obstruction and key aspects of its development mechanisms, including a detailed description of the pathogenesis of acute intestinal obstruction. It addresses problems of modern diagnostics of acute intestinal obstruction of various origins, including the worn picture of the disease, and formed optimal diagnostic and treatment algorithms. A 2018 literature review similarly considers the main etiological factors, key mechanisms of development, and problems of modern diagnostics, including the erased picture of the disease, and presents argumentation of treatment methods based on pathogenetic features.
A 2021 case report of small intestine volvulus during eight months of pregnancy states that intestinal obstruction is a topic where not all questions have been clarified and developed, and that therapy of acute obstruction is exclusively surgical.
No drug treatment is tested or proposed in any of these abstracts. What is still missing is any controlled clinical trial of a pharmacological intervention for intestinal obstruction, a clear patient stratification strategy that accounts for the phasic disruption of homeostasis seen in animal models, and funding to move from descriptive pathophysiology to interventional studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
World Journal of Gastroenterology · 2014 · 11 citations · open access
Phasic study of intestinal homeostasis disruption in experimental intestinal obstruction
AbstractAIM: To investigate the phasic alteration of intestinal homeostasis in an experimental model of intestinal obstruction. METHODS: A rabbit model of intestinal obstruction was established by transforming parts of an infusion set into an in vivo pulled-type locking clamp and creating a uniform controllable loop obstruction in the mesenteric non-avascular zone 8 cm from the distal end of the ileum. The phasic alteration of intestinal homeostasis was studied after intestinal obstruction. The changes in goblet cells, intraepithelial lymphocytes, lamina propria lymphocytes, and intestinal epithelium were quantified from periodic acid-Schiff-stained sections. Ornithine decarboxylase (ODC) activity and serum citrulline levels were measured by high-performance liquid chromatography. Claudin 1 mRNA expression was examined by real-time polymerase chain reaction analysis. Intestinal microorganisms, wet/dry weight ratios, pH values, and endotoxin levels were determined at multiple points after intestinal obstruction. Furthermore, the number and ratio of CD3(+), CD4(+) and CD8(+) T cells were determined by flow cytometry, and secretory IgA levels were measured with an enzyme-linked immunosorbent assay. RESULTS: A suitable controllable rabbit model of intestinal obstruction was established. Intestinal obstruction induced goblet cell damage and reduced cell number. Further indicators of epithelial cell damage were observed as reduced serum citrulline levels and claudin 1 gene expression, and a transient increase in ODC activity. In addition, the wet/dry weight ratio and pH of the intestinal lumen were also dramatically altered. The ratio of Bacillus bifidus and enterobacteria was reversed following intestinal obstruction. The number and area of Peyer's patches first increased then sharply decreased after the intestinal obstruction, along with an alteration in the ratio of CD4/CD8(+) T cells, driven by an increase in CD3(+) and CD8(+) T cells and a decrease in CD4(+) T cells. The number of lamina propria lymphocytes also gradually decreased with prolonged obstruction. CONCLUSION: Intestinal obstruction can induce disruption of intestinal homeostasis.
Zenodo (CERN European Organization for Nuclear Research) · 2017 · 3 citations · open access
Structural-Analytical Approach To The Problem Of Acute Intestinal Nonprovenability In Practice Of A Doctor-Clinicist. Modern Interpretation Of Mechanisms Of Development And Dissemination Of A Series Of Effective Treatment-Diagnostic Tactics
AbstractThis literature review describes the main etiological factors of intestinal obstruction, a number of key aspects of the development of intestinal obstruction mechanisms. A detailed description of the pathogenesis of acute intestinal obstruction. The problems of modern diagnostics of acute intestinal obstruction of various origins, including the worn picture of the disease on the basis of what the optimal diagnostic and treatment algorithms were formed.
Kazan medical journal · 2021 · 0 citations · open access
A case of volvulus of the small intestine during eight months of pregnancy
AbstractIntestinal obstruction is one of the chapters of modern surgery, where not all questions have yet been clarified and developed, which can be seen at least from the fact that this topic is the subject of discussion at the congresses and does not leave the pages of the surgical press. One thing is certain that the therapy of acute obstruction is exclusively surgical.
Zenodo (CERN European Organization for Nuclear Research) · 2018 · 0 citations · open access
Key Mechanisms Of The Emergence Of Acute Intestinal Obstruction And Selection Argumentation Of Therapeutic And Diagnostic Tactics (Literature Review)
AbstractIn this literature review, the main etiological factors of intestinal obstruction, key aspects of a number of mechanisms of development of intestinal obstruction are considered. The problems of modern diagnostics of acute intestinal obstruction of various genesis are considered, including the erased picture of the disease on the basis of which the optimal therapeutic diagnostic algorithms were formed. The argumentation of methods of treatment proceeding from pathogenetic features of the given pathology results.
Fecal impaction following methadone ingestion simulating acute intestinal obstruction
AbstractA hitherto unreported clinical entity, namely fecal impaction following methadone ingestion simulating acute intestinal obstruction, is described. Five cases admitted to the Surgical Service of the Beth Israel Medical Center in New York City are discussed. The nature and pathogenesis of the obstruction are analyzed and a suggested method of managing these cases is presented. It is emphasized that with expansion and increasing acceptance of Methadone Maintenance Treatment Programs, the number of such cases will increase. It is thus important that physicians become aware of the existence of this syndrome since involvement in methadone maintenance may be a life-long commitment for persons involved, thus increasing the incidence of the complication. It is also imperative to avoid unnecessary, and possibly harmful surgical intervention in such cases.
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.
