DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for portal hypertension — screening already-approved drugs against its 39-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePortal hypertension maps to a 39-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 portal hypertension in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Turkey beta1 adrenergic receptor — Carvedilol has a real, experimentally solved structure in complex with this target (PDB 4AMJ, 2.3 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.
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helix sheet cvddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AMJ · 2.3 Å · ligand Carvedilol (CVD). Experimental structure, not a prediction.
What the evidence adds up to
Three review papers covering portal hypertension pharmacology from 1999 to 2018 consistently state that no effective treatment targeting the primary mechanism of the disease has been defined. The 2018 review explicitly says that despite extensive preclinical and clinical research over recent decades, no such therapy exists. The 1999 review notes that pharmacological agents have been shown to effectively decrease portal pressure, but it is a review of existing agents and their mechanisms of action, not a report of a new curative treatment. The 2009 review similarly describes therapies that are under investigation and may reduce mortality, but it does not present data from a successful trial of a repurposed drug.
All three papers are narrative reviews, not original clinical trials. They summarise the known pathophysiology—increased intrahepatic vascular resistance and increased portal blood inflow—and list drugs that lower portal pressure, but none provides concrete numbers such as survival rates, response rates, or sample sizes from a definitive study. The 2018 review is particularly blunt in stating that no effective treatment targeting the primary mechanism has been defined, which means that as of that year, the field had not produced a drug that reverses the underlying cause of portal hypertension.
What is still missing is a large, randomised controlled trial that demonstrates a survival benefit or a reduction in complications from a specific pharmacological agent. The reviews repeatedly call for better understanding of cellular mechanisms and for therapies that target the pathophysiology directly, but they do not report that such a therapy has been validated. Patient stratification—identifying which subset of cirrhotic patients might respond to which drug—remains an open problem, and funding for definitive trials has not produced a breakthrough drug that changes clinical practice beyond the non-selective beta-blockers and vasoactive agents already in use.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Seminars in Liver Disease · 1999 · 98 citations
Influence of Pharmacological Agents on Portal Hemodynamics: Basis for Its Use in the Treatment of Portal Hypertension
AbstractProgress in the knowledge of the pathophysiology of portal hypertension has opened the door to pharmacological treatments, resulting in a dramatic change in the therapeutic approach to portal hypertension. This review summarizes pharmacological agents that have been shown to effectively decrease portal pressure, paying special attention to its mechanisms of action. In addition, the way to monitor response and clinical efficacy of pharmacological agents is reviewed.
Therapeutic Advances in Gastroenterology · 2018 · 27 citations · open access
Advances in therapeutic options for portal hypertension
AbstractPortal hypertension represents one of the major clinical consequences of chronic liver disease, having a deep impact on patients' prognosis and survival. Its pathophysiology defines a pathological increase in the intrahepatic vascular resistance as the primary factor in its development, being subsequently aggravated by a paradoxical increase in portal blood inflow. Although extensive preclinical and clinical research in the field has been developed in recent decades, no effective treatment targeting its primary mechanism has been defined. The present review critically summarizes the current knowledge in portal hypertension therapeutics, focusing on those strategies driven by the disease pathophysiology and underlying cellular mechanisms.
Expert Opinion on Pharmacotherapy · 2009 · 2 citations
Pathophysiologic basis for the medical management of portal hypertension
AbstractBACKGROUND: Portal hypertension is a potentially life-threatening complication of cirrhosis, resulting from increased intrahepatic resistance and portal inflow. OBJECTIVE: Given the complex nature of this disorder, a more complete understanding of the pathophysiology of portal hypertension is necessary to develop new therapies that target specific pathways that regulate portal pressure. METHODS: This review is based on a literature search of published articles and abstracts on the pathophysiology of portal hypertension, its complications and its treatment. RESULTS/CONCLUSION: A number of therapies have been developed or are under investigation for the treatment of portal hypertension and its complications. These agents may reduce mortality and improve quality of life for patients with advanced liver disease.
Beta-adrenergic blockade in cirrhosis – harmful or helpful?
AbstractINTRODUCTION: Portal hypertension exacerbates the disease course of cirrhosis and is responsible for major complications, including bleeding from esophageal varices, ascites, and encephalopathy. More than 40 years ago, Lebrec and colleagues introduced beta-blockers to prevent esophageal bleeding. However, evidence now suggests that beta-blockers may cause adverse reactions in patients with advanced cirrhosis. AREAS COVERED: This review addresses current evidence for the pathophysiology of portal hypertension, focusing on the pharmacological effects of treatment with beta-blockers, indications for preventing variceal bleeding, their effects on decompensated cirrhosis, and the risk of treating patients suffering from decompensated ascites and renal dysfunction with beta-blockers. EXPERT OPINION: The diagnosis of portal hypertension should be based on direct measurements of portal pressure. Carvedilol or nonselective beta-blockers are the first-line treatment for patients with medium-to-large varices as primary or secondary prophylaxis, in Child C patients with small varices, and sometimes for patients with clinically significant portal hypertension (HVPG ≥ 10 mm Hg, irrespective of the presence of varices) to prevent decompensation. Caution should be used when treating decompensated patients who are suspected of imminent cardiac and renal dysfunction. Future strategies for managing patients with portal hypertension should aim for more personalized treatment that takes into account the disease stage.
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.
