DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for gastroesophageal reflux disease — screening already-approved drugs against its 43-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGastroesophageal reflux disease maps to a 43-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
Structures already discussed alongside gastroesophageal reflux disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Structure of P450 BM3 A82F F87V — Omeprazole has a real, experimentally solved structure in complex with this target (PDB 4O4P, 1.83 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 1c6drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4O4P · 1.83 Å · ligand Omeprazole (1C6). Experimental structure, not a prediction.
What the evidence adds up to
In a 1983 randomised controlled trial of 25 patients, cimetidine 1.0 g/day did not produce a statistically significant beneficial effect compared with placebo for heartburn, antacid use, endoscopic healing, histological improvement, or acid perfusion test response. A 1991 study of 125 patients with heartburn and acid regurgitation but no endoscopic abnormalities found that cimetidine suspension 200 mg four times daily was significantly more effective than placebo at two weeks, though the placebo suspension itself had a considerable effect on symptoms.
A 1992 decision analysis using published data and an expert panel estimated that omeprazole therapy produced the lowest expected overall payments for medical care and the most symptom-free months over a 7-month model for patients with persistent grade 2 or higher reflux disease. Omeprazole was consistently about $1800 less costly than ranitidine and $2700 less costly than phase 1 therapy alone, even when payments for major complications were reduced by 80%. The analysis concluded omeprazole was the preferred initial approach but noted that assessment of long-term outcomes required extended clinical studies.
A 2000 randomised double-blind study of 201 patients with mild reflux oesophagitis compared pantoprazole 20 mg daily with ranitidine 300 mg daily. After 2 weeks, 80% of pantoprazole patients had complete relief from key symptoms versus 51% on ranitidine; after 4 weeks the figures were 88% versus 58%. Endoscopic healing after 4 weeks was 84% for pantoprazole versus 55% for ranitidine, and by 8 weeks cumulative healing was 95% versus 78%. A 2004 multicentre double-blind study of 227 patients with Los Angeles grade B/C oesophagitis found that 40 mg pantoprazole and 40 mg esomeprazole were equivalent: overall healing was 88% in both groups, and symptom relief was 55% versus 51%. A 1998 crossover study of only 5 patients with grade II oesophagitis suggested that lansoprazole 30 mg reduced total reflux time and upright reflux time significantly by day 2, while omeprazole 20 mg did not, but the authors stressed the study was limited by the very small sample.
A 2013 commentary on a comparison of pantoprazole magnesium with esomeprazole noted that about 10% of gastroesophageal reflux disease patients remain unresponsive to proton pump inhibitors at maximal doses, suggesting that resistant disease may involve a motility or other disorder not treatable by acid suppression alone. The commentary also pointed out that the 2005 EXPO study found pantoprazole sodium less effective than esomeprazole in healing reflux in Helicobacter pylori-negative patients, and that the proportion of H. pylori-positive patients in the 2013 study was not reported. A 2014 study of 40 patients reported that rabeprazole combined with hydrotalcid led to reflux symptom disappearance in 95% of patients versus 70% for omeprazole plus amoxicillin, and oesophageal pH below 4 in 10% versus 25%, but the sample was small and the comparator regimen is not a standard proton pump inhibitor monotherapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Internal Medicine · 1992 · 86 citations
Cost and Quality Effects of Alternative Treatments for Persistent Gastroesophageal Reflux Disease
AbstractBACKGROUND: Gastroesophageal reflux disease is commonly encountered by general internists and gastroenterologists. METHODS: We used decision analysis to assess the clinical and economic effects of three treatments--phase 1 therapy alone or combined with omeprazole or ranitidine hydrochloride therapy--for patients with persistent, symptomatic grade 2 or higher gastroesophageal reflux disease. To the maximum extent possible, data were obtained from the published literature. We convened an expert consensus panel to estimate specific data points when they were unavailable or contradictory in the literature, including estimates of optimal and actual clinical practice patterns. A 7-month model was used to correspond to the time frame of available clinical trial data. The perspective of the analysis was that of the payer. The costs of medical care for various clinical outcomes were based on actual mean payments made by Independence Blue Cross of Philadelphia and Pennsylvania Blue Shield. RESULTS: Although the retail payments for daily omeprazole therapy are the highest among the three interventions tested, it produced both the lowest expected overall payments for medical care and the most effective strategy for treating symptoms during the 7-month model. Omeprazole therapy was consistently approximately $1800 less costly than ranitidine therapy and $2700 less costly than phase 1 therapy alone during the period examined, regardless of whether empiric or nonempiric treatment strategies were used. Even when payments for major complications (the most important cost variable) were reduced by 80%, omeprazole therapy resulted in payments 17% and 22% lower than those associated with ranitidine therapy and phase 1 therapy alone, respectively. Omeprazole also produced the most symptom-free months during the 7-month follow-up period. The clinical and economic outcomes of performing an initial diagnostic workup, compared with treating patients empirically, were equal. CONCLUSIONS: We conclude that omeprazole therapy is the preferred initial therapeutic approach for patients with persistent, symptomatic gastroesophageal reflux disease in whom phase 1 therapy fails. Assessment of long-term approaches must await the results of extended clinical studies.
Journal of Clinical Gastroenterology · 2004 · 66 citations
40 mg Pantoprazole and 40 mg Esomeprazole Are Equivalent in the Healing of Esophageal Lesions and Relief from Gastroesophageal Reflux Disease???related Symptoms
AbstractBACKGROUND: Proton pump inhibitors are regarded as the most effective class of acid suppressive medication for gastroesophageal reflux disease treatment. There is considerable interest regarding the dose equivalence between various proton pump inhibitors. GOALS: To compare the efficacy of pantoprazole and esomeprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. STUDY: Multicenter, randomized, double-blind study. Patients with gastroesophageal reflux disease grades B/C (Los Angeles classification) received 40 mg pantoprazole daily (n = 113) or 40 mg esomeprazole daily (n = 114). Healing (endoscopy) and relief from gastroesophageal reflux disease-related symptoms (direct questioning) were assessed at first and final visit (after 4, 6, 8, or 10 weeks of treatment). RESULTS: Overall healing in both treatment groups was 88% of patients (intention-to-treat population), 95% (pantoprazole), and 90% (esomeprazole) (per-protocol population); statistically, this indicates "at least equivalence" between treatments. Overall relief from gastroesophageal reflux disease-related symptoms was similar for pantoprazole (55%) and esomeprazole (51%, per-protoco). No correlation between healing and symptom relief was seen. The majority of reported adverse events were assessed as "not related" to the study drug. Pantoprazole and esomeprazole have comparably good safety and tolerability. CONCLUSION: In patients with gastroesophageal reflux disease, 40 mg pantoprazole daily and 40 mg esomeprazole daily are equally effective for healing of esophageal lesions and relieving gastroesophageal reflux disease-related symptoms.
European Journal of Gastroenterology & Hepatology · 2000 · 43 citations
Efficacy and tolerability of 20 mg pantoprazole versus 300 mg ranitidine in patients with mild reflux-oesophagitis
AbstractBACKGROUND AND AIM: The aim of this study was to compare the efficacy and tolerability of low dose pantoprazole (20 mg) (a gastric proton pump inhibitor) with standard dose ranitidine (300 mg) (a histamine-receptor antagonist), in their ability to relieve symptoms and heal oesophageal lesions associated with gastrooesophageal reflux disease (GORD). METHODS: Patients with endoscopically established mild GORD (stage I, modified Savary-Miller classification) were enrolled into a multicentre, randomized, double-blind, parallel-group comparison study (intention-to-treat population, n = 201; age range, 18-82 years). Patients took either oral pantoprazole 20 mg in the morning (n = 101) or ranitidine 300 mg in the evening (n = 100) once daily for 4 weeks or, if the healing was not complete, 8 weeks. Relief from key symptoms (heartburn, acid regurgitation, pain on swallowing) was assessed after 2, 4, and if applicable, 8 weeks. Healing of lesions was confirmed endoscopically after 4 and, if applicable, 8 weeks. RESULTS: Complete relief from key symptoms was noted after 2 weeks in 70/88 (80%) patients treated with pantoprazole vs 45/89 (51%) patients treated with ranitidine ('per-protocol and key-point available' populations, P < 0.001); the corresponding results after 4 weeks were 77/88 (88%) vs 51/88 (58%) (P < 0.001). Complete healing of lesions after 4 weeks of treatment was seen in 74/88 (84%) vs 49/89 (55%) in the pantoprazole and ranitidine group, respectively (P < 0.001, per-protocol); by week 8 the cumulative healing rates were 84/88 (95%) vs 69/89 (78%) in the pantoprazole and ranitidine group, respectively (P < 0.001). For the intention-to-treat populations, the corresponding values for healing after 4 and 8 weeks were 73% vs 49% (P < 0.001) and 83% vs 69% (P < 0.05), respectively. Both study medications were well tolerated. CONCLUSION: Compared to ranitidine 300 mg, the regimen with pantoprazole 20 mg provides faster relief from symptoms and is significantly more effective in healing of oesophageal lesions in patients with mild reflux-oesophagitis. Thus, the low dose of pantoprazole offers a treatment approach which minimizes drug exposure and costs while retaining high efficacy.
The Medical Journal of Australia · 1983 · 17 citations
Treatment of reflux oesophagitis: A randomized, controlled evaluation of cimetidine
AbstractTwenty-five patients were studied in an eight-week randomized controlled comparison of cimetidine and placebo in the treatment of reflux oesophagitis. Therapy with cimetidine (1.0 g/day), compared with placebo, did not produce a statistically significant beneficial effect as assessed by relief of heartburn, reduction in antacid use, endoscopic evidence of healing, histological signs of improvement, or response to the acid perfusion (Bernstein) test.
Cimetidine suspension in patients with Stage 0 gastro‐oesophageal reflux disease
AbstractOne hundred and twenty-five patients with symptoms of heartburn and acid regurgitation but without endoscopic abnormalities were randomized to receive 200 mg cimetidine suspension four times daily or placebo for two weeks. Daily dairy cards were kept to evaluate the frequency and degree of symptoms. At two weeks cimetidine was significantly more effective than placebo. It is concluded that placebo suspension has a considerable effect on gastro-oesophageal reflux disease symptoms, but cimetidine suspension provides significantly better relief.
European Journal of Gastroenterology & Hepatology · 1998 · 3 citations
Speed of onset of oesophageal acid reduction with different proton-pump inhibitors in patients with reflux oesophagitis
AbstractOBJECTIVE: Proton-pump inhibitors are the most effective drug treatment for gastro-oesophageal reflux disease. With the increasing trend toward 'on demand' therapy, it is important to determine how quickly oesophageal acid reflux is reduced, and whether this differs between the available compounds. DESIGN: A 2 x 2 double-blind crossover study. METHOD: Eight patients with Savary-Miller grade II oesophagitis underwent 24 h pre-treatment oesophageal pH monitoring. Each patient was randomly allocated to receive daily omeprazole 20 mg and lansoprazole 30 mg for 2 days, in two separate double-blind periods, with a washout period of 14 days. Two further oesophageal pH recordings were obtained during the second 48 h period of treatment with each drug. RESULTS: Five patients completed the study and their results are presented. Lansoprazole significantly reduced the percentage of total reflux time (P = 0.04) and percentage upright reflux time (P=0.04) on the second day of treatment compared to the pre-treatment, while this was not achieved with omeprazole. There was a significant difference in the reduction of the total reflux time (P= 0.011), upright reflux time (P=0.021) and total reflux episodes (P < 0.001) on day 2 of treatment when comparing lansoprazole with omeprazole. All patients on lansoprazole had a decrease in symptoms of heartburn and regurgitation, with complete resolution in four patients. Three patients had a decrease in these symptoms with omeprazole, including complete resolution in two. CONCLUSION: This study was limited by the small number of patients who underwent this demanding investigation. However, lansoprazole appears to have a more rapid onset of reduction of acid gastro-oesophageal reflux than omeprazole over a 48 h period.
Commentary: daily pantoprazole vs. esomeprazole for GERD
AbstractSome comparisons of pantoprazole sodium with esomeprazole in health and disease have shown a slight superiority in favour of esomeprazole with regard to raising intragastric pH.1, 2 Others have shown little difference in bioavailability and pharmacokinetics when assessed on the 7th day of dosing.3 The study by Moraes-Filho et al. compares a new pantoprazole magnesium compound with esomeprazole in patients with mostly mild (Los Angeles grade A 60%) gastro-oesophageal reflux disease (GERD).4 There was little difference in terms of symptom relief as assessed by re QUEST-GI at 4 weeks and endoscopy, but when treatment was continued for a further 4 weeks in nonresponders a marginal superiority of pantoprazole magnesium was detected. The authors attribute this late effect to the unique pharmacokinetics of pantoprazole magnesium. In this, and in many other studies, about 10% of GERD patients remain unresponsive to proton pump inhibitors prescribed at maximal doses, suggesting that patients with resistant disease may have an associated motility or other disorder that requires a strategy that is not based solely on suppression of gastric acidity. In the 2005 large EXPO study,5 it was found that pantoprazole sodium was less effective than esomeprazole in healing GERD in patients who were Helicobacter pylori-negative. In this present study, no data on the proportion of the patients in each treatment group colonised by H. pylori was provided. If there is a relatively high prevalence of H. pylori in Brazil the difference noted at the end of 8 weeks could be due to an unbalanced distribution of H. pylori-positive patients in the study groups. ‘Evergreening’ is a process by which successful drugs are altered and the difference between the old and new compounds exaggerated to protect patents.6 An example is when single enantiomer compounds are promoted over older racemic varieties.7 However, it is not clear from this article that pantoprazole magnesium is sufficiently different from pantoprazole sodium for evergreening to be applicable. Declaration of personal and funding interests: None.
Analysis on treatment efficacy of hydrotalcid combined with rabeprazole in treating gastroesophageal reflux disease
AbstractObjective To evaluate the clinical efficacy of rabeprazole combined with aluminum magnesium in gastroesophageal reflux disease treatment.Methods From August 2010 to October 2013 in our hospital,40 cases of gastroesophageal reflux disease were randomly divided into two groups,20 cases in observation group,using aluminum magnesium rabeprazole combination therapy,the control group with 20 cases used omeprazole amoxicillin treatment,the degree of improvement in reflux symptoms and esophageal pH changes in two groups were compared after 4 weeks.Results The reflux symptoms disappeared in 19 patients (95％),reflux symptoms did not disappear in 1 case (5％) in the control group reflux symptoms disappeared in 14 patients (70％),reflux symptoms did not disappear in 6 patients (30％),two reflux symptom improvement was statistically significantly different (P ＜ 0.05).In observation group 2 patients (10％) esophageal pH ＜ 4,18 patients (90％) esophageal pH ＞ 4,the control group 5 cases (25％) esophageal pH ＜ 4,15 patients (75％) pH ＞ 4,two esophagus pH changes showed statistical significant differences (P ＜ 0.05).Conclusion The combined aluminum magnesium rabeprazole therapy has good clinical efficacy in the treatment of gastroesophageal reflux disease,deserves to be promoted in clinical practice.
Key words:
Rabeprazole; Hydrotalcid; Gastroesophageal reflux disease
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, 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.
