DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for dyspepsia — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDyspepsia maps to a 37-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 dyspepsia 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
dopamine receptor D2 (DRD2) — DRD2 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 8alphadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9BS9 · 2.28 Å · ligand (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide (7LD). Experimental structure, not a prediction.
What the evidence adds up to
A population-based survey of 351 dyspeptic subjects found that distinct subgroups exist in the community: 51% reported frequent upper abdominal pain, 47% early satiety, and 21% nausea or vomiting, with overlap between these groups significantly less than expected by chance. The authors concluded that separate evaluation and treatment strategies are needed. A 2016 review notes that functional dyspepsia affects 10% of the population and that the Rome IV criteria further emphasise the subtypes of postprandial distress syndrome and epigastric pain syndrome, while concluding that gastroesophageal reflux disease and irritable bowel syndrome are part of the functional dyspepsia spectrum. The review also reports that new data implicate herbivore pets and antibiotic exposure in pathogenesis, but states these findings require confirmation.
A 1994 double-blind randomised Swiss multicentre study compared the prokinetic drug cisapride (5 mg four times daily) with the histamine H2-receptor antagonist cimetidine (200 mg four times daily) in 137 patients with functional dyspepsia. After four weeks, a small but significant difference in favour of cisapride was found, mainly accounted for by the dysmotility-like subtype, where 83% improved with cisapride versus 59% with cimetidine. No significant differences were detected between the drugs in the other dyspepsia subtypes at the end of treatment or follow-up. The study confirmed classification into dyspepsia subtypes as a useful tool in selecting drug therapy.
A 2002 assessment of outcome measures in dyspepsia states that there is a lack of consensus among researchers on how to best measure outcome in functional dyspepsia trials and a lack of validated outcome measures. It notes that if symptoms resolve completely, treatment has been successful, but with partial improvement interpretation is less straightforward. A 2006 study of 63 duodenal ulcer patients and 62 non-ulcer dyspepsia patients in Turkey found that seropositivity for anti-CagA was 82% and 87% respectively, and for anti-VacA was 40% and 25% respectively, concluding that none of these virulence factors was associated with the development of duodenal ulcer in the studied patients.
What is still missing is a consensus on validated outcome measures for functional dyspepsia trials, as noted in 2002, and the 2016 review indicates that the pathogenesis remains incompletely understood, with environmental factors requiring confirmation. The 1994 trial is decades old and tested drugs that are not standard current therapy; no recent randomised controlled trial data for a drug therapy in dyspepsia are provided in these abstracts.
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 American Journal of Gastroenterology · 2007 · 90 citations
Do Distinct Dyspepsia Subgroups Exist in the Community? A Population-Based Study
AbstractBACKGROUND: The heterogeneity of the dyspepsia symptom complex is well known. Several attempts to classify dyspepsia into subgroups have been proposed as a basis for diagnosis and therapy, but data are conflicting. We postulated that dyspepsia comprises three distinct subsets, characterized by pain, early satiety, or nausea/vomiting. We aimed to identify these subsets of dyspepsia: "frequent upper abdominal pain (UAP),""early satiety (ES)," and "nausea/vomiting (NV)." METHODS: A population-based, cross-sectional survey study was conducted by mailing a valid questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN, aged 20-94 yr (response rate 55%). Dyspepsia and irritable bowel syndrome (IBS) prevalence were estimated by Rome II criteria; gastroesophageal reflux (GERD) by weekly or more frequent heartburn or acid regurgitation. Dyspepsia subgroups were categorized based on a priori defined symptoms. RESULTS: The prevalence (95% CI) of dyspepsia was 15% (14, 17). Of 351 dyspeptic subjects, 51% (46, 56) reported UAP, 21% (16, 25) NV, and 47% (42, 52) ES. The overlap of the subgroups was significantly less than expected by chance. Among the three groups, the subjects were similar in age, educational level, IBS status, and overall symptom severity. A high somatic symptom checklist score and those with GERD were associated with greater odds for reporting combination symptoms compared with the upper abdominal pain subgroup of dyspepsia or the early satiety subgroup of dyspepsia, respectively. CONCLUSION: Distinct subgroups of uninvestigated dyspepsia do exist in the general population, suggesting that separate evaluation and treatment strategies are needed.
Current Opinion in Gastroenterology · 2016 · 74 citations
Functional dyspepsia
AbstractPURPOSE OF REVIEW: Functional dyspepsia affects 10% of the population. Emerging data are beginning to unravel the pathogenesis of this heterogeneous disorder, and new data on treatment are helping to guide evidence-based practice. In this review, the latest advances are summarized and discussed. RECENT FINDINGS: The Rome IV criteria were published in 2016 and are similar to Rome III but further emphasize the subtypes (postprandial distress syndrome and epigastric pain syndrome) rather than focussing on the syndrome as a whole, and conclude that gastroesophageal reflux disease and irritable bowel syndrome are part of the functional dyspepsia spectrum. Environment is dominant in the pathogenesis. New data implicate herbivore pets and antibiotic exposure for a nongastrointestinal infection but require confirmation. Further experimental data suggest duodenal eosinophils and mast cells can alter enteric neuronal structure and function in functional dyspepsia. SUMMARY: Advances in our understanding of functional dyspepsia are changing clinical practice.
Scandinavian Journal of Gastroenterology · 1994 · 32 citations
Cisapride or Cimetidine in the Treatment of Functional Dyspepsia: Results of a Double-Blind Randomized, Swiss Multicentre Study
AbstractBACKGROUND: Functional dyspepsia is a major diagnostic and therapeutic challenge for the clinician. Several systems for the identification of 'high-risk' patients and classifications of dyspepsia subtypes and treatment schemes have been proposed in the past with limited experimental evidence to support the claims made. The present trial was designed to compare two different treatment modalities in a group of functional dyspepsia patients selected on the basis of a standardized diagnostic procedure as 'non-risk' for organic disease and to assess the result in the major symptom sub-groups of functional dyspepsia as a means of identifying the potential for improving treatment outcome. METHODS: The efficacy of the prokinetic drug cisapride (5 mg four times daily) and of the histamine H2-receptor antagonist cimetidine (200 mg four times daily) were evaluated after 1 month of treatment and after a further follow-up of 1 month. Patients were randomized to the trial if they fulfilled the following criteria: 1) 'low-risk' symptoms or negative endoscopy findings, and 2) 2 weeks of single-blind antacid treatment did not provide satisfactory relief. For analysis patients were stratified into dyspepsia subtypes. RESULTS: One hundred and sixty-one patients entered the run-in period, and 137 patients were randomized to the study. At the end of 4 weeks' treatment a small but significant difference in favour of cisapride was found; this difference can mainly be accounted for by the significant difference found in the dysmotility-like subtype (83% improved with cisapride versus 59% with cimetidine). No significant differences could be detected between drugs in the other dyspepsia subtypes at the end of the treatment-or follow-up period. CONCLUSIONS: The study confirms the classification into dyspepsia-subtypes as a useful tool in selecting the most appropriate drug therapy.
Assessment of outcome in dyspepsia: has progress been made?
AbstractThere is a lack of consensus among researchers on how to best measure outcome in functional dyspepsia trials and more importantly a lack of validated outcome measures. If symptoms resolve completely, treatment has been successful but with partial improvement interpretation is less straightforward. It is most likely that these issues will only be resolved if unequivocally efficacious treatments emerge to which the different outcome measures can be compared. Recently, a few validated outcome measures have been developed which look promising.
World Journal of Gastroenterology · 2006 · 9 citations · open access
Analysis of serum antibody profile against<i>H pylori</i>VacA and CagA antigens in Turkish patients with duodenal ulcer
AbstractAIM: To investigate the frequency of seropositivity against CagA, VacA proteins and to determine their independent effects on the development of duodenal ulcer (DU) in Turkish patients. METHODS: The study was designed as a prospective one from a tertiary referral hospital. Dyspeptic patients who were referred to our endoscopy unit for upper gastrointestinal endoscopy between June 2003 and March 2004 and diagnosed to have DU or nonulcer dyspepsia (NUD) were included. Biopsies from the antrum and body of the stomach were taken in order to assess the current H pylori status by histology, rapid urease test and culture. Fasting sera were obtained from all patients and H pylori status of all sera was determined by IgG antibodies using an enzyme-linked immunosorbent assay (ELISA) kit. All seropositive patients were further analysed using Western blot assays detecting IgG antibodies against CagA and VacA proteins. The c2 test was used for statistical comparison of the values and age-sex adjusted multiple regression analysis was used to determine the independent effects of CagA and VacA seropositivities on the development of DU. RESULTS: Sixty-three patients with DU and 62 patients with NUD were eligible for the final analysis. Seropositivity for anti-CagA was detected in 51 of 62 (82%), and in 55 of 63 (87%) patients with NUD and DU, respectively (P = no significance), and seropositivity for anti-VacA was found in 25 of 62 (40% ) and in 16 of 63 (25%) patients, with NUD and DU, respectively. CONCLUSION: These findings suggest that none of these virulence factors is associated with the development of DU in the studied Turkish patients with dyspepsia.
Gastroenterologie a hepatologie · 2024 · 0 citations
Cinitaprid expands treatment options for functional dyspepsia
Abstractreatment of functional dyspepsia is often medically difficult and requires a comprehensive approach, including the drug group prokinetics. In the Czech Republic, it is now being expanded to include the active substance cinitapride. The presented text summarizes its basic pharmacological properties and summarizes the available relevant aspects of its clinical use.
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.
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