DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for endocrine pancreas disorder — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEndocrine pancreas disorder maps to a 1-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 endocrine pancreas disorder 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 cAMP-dependent type I regulatory subunit alpha (PRKAR1A) — PRKAR1A 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 pcgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5KJZ · 1.347 Å · ligand CYCLIC GUANOSINE MONOPHOSPHATE (PCG). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not report any drug repurposing trials, clinical outcomes, or patient-level efficacy data for endocrine pancreas disorders. A 2004 review of pancreatic endocrine tumours notes that octreotide has antiangiogenic properties and that tyrosine kinase receptors such as c-kit, epidermal growth factor receptor, and platelet-derived growth factor receptor are overexpressed on malignant endocrine pancreatic tumours, suggesting these receptors might be pharmacologic targets, but no clinical results from such targeting are given. The same review identifies chromogranin A as a promising marker and mentions improved imaging with F-dopa PET and laparoscopic ultrasound, but no drug response rates or survival figures are cited.
A 2013 review of pancreatic secretion discusses ghrelin and somatostatin receptor signalling in glucose-stimulated insulin secretion, and notes that endoplasmic reticulum stress and loss-of-function mutations of a key ER stress protein reduce insulin secretion. No therapeutic interventions are tested. A 2016 review of pancreas transplantation in unconventional recipients reports that obesity is detrimental to graft survival and that data on transplantation in patients with HIV or hepatitis C yield mixed outcomes, but this is surgical, not pharmacological.
The remaining abstracts cover developmental biology (2017, 2012), trace element changes in pancreatitis (2009), and a general overview of pancreatic secretion (2013). None contain numbers for survival, response, or sample sizes. What is missing is any clinical trial testing a repurposed drug in patients with endocrine pancreas disorders, any randomised controlled data, any stratification of patients by molecular subtype, and any funding for such work.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Development · 2017 · 182 citations
Cellular and molecular mechanisms coordinating pancreas development
AbstractThe pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer.
Current Opinion in Gastroenterology · 2013 · 51 citations · open access
Modulation of pancreatic exocrine and endocrine secretion
AbstractPURPOSE OF REVIEW: Recent advances in the regulation of pancreatic secretion by secretagogues, modulatory proteins and neural pathways are discussed. RECENT FINDINGS: Downstream events involved in secretagogue stimulation of pancreatic secretion have been elucidated through characterization of the Src kinase pathway. An additional mechanism regulating vagus nerve effects on the pancreas involves Group II and III metabotropic glutamate receptors that are located presynaptically on certain vagal pancreas-projecting neurons. Hypothalamic neurons perceive glucose and regulate insulin release by direct communication with islets, and activation of proopiomelanocortin neurons by leptin enhances insulin secretion and modulates glucose but not energy homeostasis. Ghrelin and somatostatin mediate glucose-stimulated insulin secretion by differential receptor signaling that is dependent on the amount of ghrelin and state of receptor heterodimerization. Endoplasmic reticulum (ER) stress and loss-of-function mutations of a key ER stress protein are associated with disruption of membrane translocation and reduction in insulin secretion. The importance of hormones, neuropeptides, amino acids, cytokines and regulatory proteins in pancreatic secretion and the pathophysiology of type 2 diabetes are also discussed. SUMMARY: The biomolecular pathways regulating pancreatic secretions are still not fully understood. New secretagogues and mechanisms continue to be identified and this information will aid in drug discovery and development of new and improved therapy for pancreatic disorders.
Association of fatty pancreas with pancreatic endocrine and exocrine function
AbstractAIM: The purpose of this study was to clarify whether fatty pancreas might lead to impaired pancreatic endocrine or exocrine function. MATERIAL AND METHODS: The study involved 109 participants who had undergone the glucagon stimulation test and N-benzoyl-L-tyros-p-amino benzoic acid (BT-PABA) test to assess pancreatic function as well as unenhanced abdominal computed tomography (CT). Pancreatic endocrine impairment was defined as ΔC peptide immunoreactivity less than 2 [mmol/L] in the glucagon stimulation test, and pancreatic exocrine impairment was defined as a urinary PABA excretion rate less than 70% on the BT-PABA test. We defined as the mean CT value of pancreas / CT value of spleen (P/S ratio) as a marker to assess fatty pancreas. We analyzed the association between fatty pancreas and pancreatic impairment using the logistic regression model. The odds ratio (OR) is shown per 0.1 unit. RESULTS: Pancreatic endocrine function was impaired in 33.0% of the participants, and 56.9% of those were regarded as having pancreatic exocrine impairment. The P/S ratio was significantly correlated with pancreatic endocrine impairment in univariate analysis (OR = 0.61, 95% confidence interval (CI) = 0.43-0.83, P = 0.0013) and multivariate analysis (OR = 0.38, 95% CI = 0.22-0.61, P < .0001) for all participants. Similar significant relationships were observed in both univariate (OR = 0.70, 95% CI = 0.49-0.99, P = 0.04) and multivariate (OR = 0.39, 95% CI = 0.21-0.66, P = 0.0002) analyses for the participants without diabetes (n = 93). The amount of pancreatic fat was not associated with exocrine impairment in univariate analysis (OR = 0.80, 95% CI = 0.59-1.06, P = 0.12). CONCLUSION: Fatty pancreas was associated with pancreatic endocrine impairment but did not have a clear relationship with pancreatic exocrine impairment.
Current advances in the diagnosis and treatment of pancreatic endocrine tumors
AbstractPURPOSE OF REVIEW: A comprehensive literature review of more than 200 original manuscripts published in the last 18 months was conducted to summarize landmark studies performed on the molecular biology, diagnosis, imaging, and treatment of endocrine tumors of the pancreas. RECENT FINDINGS: Recent achievements occurred on many fronts. Identification of a novel insulin splice variant with increased translation efficiency moved forward the understanding of the molecular biology of insulinomas. Results of a 29-year prospective study from the National Institutes of Health clarified the epidemiology of multiple endocrine neoplasia-1 syndrome. Chromogranin A was identified as a promising marker for pancreatic endocrine tumors. New imaging, including F-dopa positron emission tomography and laparoscopic ultrasound, and the effective combination of existing modalities localized and staged tumors with greater accuracy. Nonoperative treatment strategies show promise; discovery of the antiangiogenic properties of octreotide and the overexpression of tyrosine kinase receptors such as c-kit, epidermal growth factor receptor, and platelet-derived growth factor receptor on malignant endocrine pancreatic tumors may lead to promising pharmacologic treatment. SUMMARY: There have been exciting recent advancements in research surrounding endocrine pancreas that hopefully will pave the way for potential improvement in clinical outcomes for patients with these tumors.
Current Opinion in Organ Transplantation · 2016 · 15 citations
Pancreas transplantation in unconventional recipients
AbstractPURPOSE OF REVIEW: Advances in surgical technique and immunosuppression have significantly improved outcomes after pancreas transplantation, and as a result pancreas transplants increasingly are being performed for indications other than type 1 diabetes mellitus. This review summarizes the current literature on pancreas transplantation in unconventional recipient populations. RECENT FINDINGS: An increasing body of work suggests that pancreas transplantation can be performed with good outcomes in patients with type 2 diabetes mellitus and those 50 years of age and older. Obesity appears detrimental to patient and pancreas graft survival, and bariatric surgery prior to transplantation may be of increasing interest and relevance. There are limited data yielding mixed outcomes on pancreas transplantation in patients with HIV or hepatitis C virus. However, rapidly improving antiviral therapies are prolonging survival in patients with HIV and chronic hepatitis C virus infections and may increase the number of candidates available for pancreas transplantation in these populations in the future. SUMMARY: Despite limited literature in these patient populations, pancreas transplantation may be a viable treatment option for endocrine pancreas failure in appropriately selected patients regardless of disease cause or age.
Hormone Research in Paediatrics · 2012 · 12 citations
Determinants of Pancreatic Islet Development in Mice and Men: A Focus on the Role of Transcription Factors
AbstractThe development of the endocrine pancreas is regulated by several cell-matrix interactions that generate a diverse array of intracellular signals determining the progression of a multipotent progenitor to a mature endocrine cell. This process involves interactions between the epithelium, mesenchyma, and endothelial cells. Later in development, coordinated signaling contributes to the maintenance of the differentiated endocrine cell phenotype. It has been demonstrated that key factors as well as the sequence of events involved in mouse pancreatic development is conserved in humans. This review will discuss our current knowledge in mouse as well as human pancreatic development and highlights some important transcription factors associated with human disease.
Change of Zinc, Copper, and Metallothionein Concentrations and the Copper-Zinc Superoxide Dismutase Activity in Patients With Pancreatitis
AbstractPancreas provides a central forum for communication of original works involving both basic and clinical research on the exocrine and endocrine pancreas and their interrelationships and consequences in disease states. This multidisciplinary, international journal covers the whole spectrum of basic sciences, etiology, prevention, pathophysiology, diagnosis, and surgical and medical management of pancreatic diseases, including cancer.
Transplantation Direct · 2017 · 0 citations · open access
Pancreas Transplantation With Portal-Enteric Drainage for Patients With Endocrine and Exocrine Insufficiency From Extensive Pancreatic Resection
AbstractAlthough the primary indication for pancreas transplantation is type I diabetes, a small number of patients requires pancreas transplantation to manage combined endocrine and exocrine insufficiency that develops after extensive native pancreatic resection. The objective of this case report was to describe the operative and clinical course in 3 such patients and present an alternative technical approach.
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.
