DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for gastroparesis — screening already-approved drugs against its 26-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGastroparesis maps to a 26-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 gastroparesis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
neurotrophic receptor tyrosine kinase 2 (NTRK2) — NTRK2 is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has 5-{3-methoxy-4-[(4-methoxybenzyl)oxy]benzyl}pyrimidine-2,4-diamine bound in it, shown as sticks.
Loading structure…
helix sheet 4-methoxybenzyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AT5 · 1.71 Å · ligand 5-{3-methoxy-4-[(4-methoxybenzyl)oxy]benzyl}pyrimidine-2,4-diamine (MUJ). Experimental structure, not a prediction.
What the evidence adds up to
Gastroparesis is defined as delayed gastric emptying without mechanical obstruction, causing early satiety, nausea, vomiting, bloating and abdominal pain. A 2015 review states that current treatment options are empirical, palliative and often ineffective, because the motor functions and neural inputs controlling gastric motility are not fully understood. The same review notes that identification of common cellular changes in gastroparesis has provided targets for treatment, but calls this the future of therapy rather than a present reality.
A 2016 review of pharmacological safety reports that none of the medications used for gastroparesis — prokinetics, antiemetics, sensory neuromodulators and pain modifying agents — are devoid of side effects. The authors advise that the risk/benefit ratio must be considered for each patient, and that awareness of drug interactions is necessary because these agents are increasingly given in combination. The review adds that pharmacological options have been limited and sometimes less than optimal.
A 2023 review covering gastroparesis syndromes, which include chronic unexplained nausea and vomiting and functional dyspepsia, states that there remain large unmet needs. Current mainstays are diet and drugs such as dopamine receptor antagonists, 5-hydroxytryptamine receptor agonists and antagonists, neurokinin-1 receptor antagonists and other anti-emetics. The review identifies gaps in knowledge about pathophysiology as critical to developing successful therapeutic agents, and notes that the major challenges ahead are to develop genetic and biochemical correlates of recent advances in microscopic anatomy and cellular function.
No abstract reports a completed randomised trial of a repurposed drug for gastroparesis with survival or response rate data. What is missing is a clear, testable molecular target validated in patients, funding for a properly blinded trial with objective gastric emptying endpoints, and stratification of patients by the cellular or genetic abnormalities now being described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Expert Opinion on Pharmacotherapy · 2015 · 13 citations
Current advances in treatment of gastroparesis
AbstractINTRODUCTION: Gastroparesis is a syndrome defined by delayed gastric emptying in the absence of mechanical obstruction. Gastroparesis has significant symptomatology and negative impacts on the patient's quality of life. AREAS COVERED: This article reviews current treatment options for gastroparesis, recent advances in treatment and future directions that treatment may head. Current options are broadly divided into prokinetics and symptom modulators. Within each group, current modalities as well as recent advances are discussed according to agent mechanism of action. Lastly, findings regarding the cellular pathophysiology involved in gastroparesis will be briefly reviewed along with their implications for future treatments. EXPERT OPINION: The numerous motor functions and neural inputs that control gastric motility are complex and not fully understood. Our lack of understanding of its pathophysiology has led to treatment options which are empirical, palliative and often ineffective. Newly intensified interest in the cellular pathophysiology behind gastroparesis provides promise for a new era of treatments. Identification of common cellular changes in gastroparesis has provided targets for treatment that may allow us to one day better treat the symptoms of gastroparesis related to its underlying pathophysiology. This is the future of gastroparesis therapy.
Expert Opinion on Drug Safety · 2016 · 11 citations
Safety of treatment for gastroparesis
AbstractINTRODUCTION: Gastroparesis is a syndrome of chronic, often debilitating symptoms related to impaired gastric motility, resulting in delayed emptying of the stomach, within the setting of a documented absence of any mechanical obstruction in the upper gastrointestinal tract. This disorder manifests with the presence of early satiety, postprandial fullness, nausea, vomiting, bloating and abdominal pain. The past ten years have shown significant advances in knowledge of the pathophysiology of this entity as well as in new diagnostic tests. However, in the clinical world which requires treatment of gastroparetic symptoms, the pharmacological options have been limited and sometimes less than optimal. AREAS COVERED: This article provides an overview of the safety of the available pharmacological therapies utilized in the treatment of gastroparetic symptoms specifically addressing the safety of prokinetics, antiemetics, sensory neuromodulators and pain modifying agents. In addition, a brief overview of the evolving but yet to be officially approved agents is included. EXPERT OPINION: None of the medications used for the treatment of gastroparesis are devoid of side effects. Therefore, when prescribing these medications, the risk/benefit ratio should be considered. Since those agents are increasingly administered in combination, awareness of possible drug interactions must be considered in a setting of the patients' medical history, age, systemic diseases and other medications.
Journal of Nippon Medical School · 2014 · 8 citations · open access
Successful Treatment of Gastroparesis with the Antidepressant Mirtazapine: A Case Report
AbstractTreatments for gastroparesis have been unsatisfactory. We describe a patient with gastroparesis who did not respond to a series of conventional prokinetic treatments. Finally, an antidepressant, mirtazapine, was administered, and the patient's symptoms and gastric emptying showed surprisingly rapid improvement. Therefore, we recommend mirtazapine as a treatment for gastroparesis refractory to conventional treatments.
Expert Opinion on Investigational Drugs · 2023 · 6 citations
Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities
AbstractINTRODUCTION: Gastroparesis (Gp) and related disorders such as chronic unexplained nausea and vomiting and functional dyspepsia, known as gastropareis syndromes (GpS), have large unmet needs. Mainstays of GpS treatments are diet and drugs. AREAS COVERED: The purpose of this review is to explore potential new medications and other therapies for gastroparesis. Before discussing possible new drugs, the currently used drugs are discussed. These include dopamine receptor antagonists, 5-hydroxytryptamine receptor agonists and antagonists, neurokinin-1 receptor antagonists and other anti-emetics. The article also considers future drugs that may be used for Gp, based on currently known pathophysiology. EXPERT OPINION: Gaps in knowledge about the pathophysiology of gastroparesis and related syndromes are critical to developing therapeutic agents that will be successful. Recent major developments in the gastroparesis arena are related to microscopic anatomy, cellular function, and pathophysiology. The major challenges moving forward will be to develop the genetic and biochemical correlates of these major developments in gastroparesis research.
Expert Opinion on Pharmacotherapy · 2024 · 1 citations
Current and emerging pharmacotherapy for the treatment of gastroparesis
AbstractINTRODUCTION: Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of life greatly. The treatment modalities available for gastroparesis have been expanding over the past 2 decades. Currently, there are multiple options available for gastroparesis, albeit with only one FDA-approved medication until June 2021. AREAS COVERED: We review the different treatments available for gastroparesis and discuss the recently FDA-approved intranasal formulation of metoclopramide. This nasal spray guarantees metoclopramide absorption within 15 min of application bypassing first pass metabolism in the liver and overcoming the limitations of the oral formulation not passing into the small intestine for absorption because of a gastroparetic stomach or a patient unable to take the oral metoclopramide because of nausea and vomiting. EXPERT OPINION: We now find ourselves in an oasis after spending many years in a 'desert' regarding pharmacologic therapies available for gastroparesis. The expansion of the research involving dopamine receptor antagonists and delving into alternative mechanisms of alleviating gastroparesis symptoms has been crucial in the landscape of gastroparesis. This is especially true as our knowledge of gastroparesis has proven that simply improving gastric emptying does not necessarily translate to clinical improvement.
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.
