DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hepatic veno-occlusive disease — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHepatic veno-occlusive disease maps to a 5-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 hepatic veno-occlusive disease 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
serpin family C member 1 (SERPINC1) — SERPINC1 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 z9ldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3KCG · 1.7 Å · ligand methyl 2,3,6-tri-O-sulfo-alpha-D-glucopyranoside (Z9L). Experimental structure, not a prediction.
What the evidence adds up to
No pharmacologic approaches that clearly prevent or treat hepatic veno-occlusive disease have been identified as of 2000, and the biology of the syndrome remains poorly understood. A 1982 letter reports one case of reversible veno-occlusive disease attributed to 6-thioguanine in a 46-year-old man with acute leukaemia in remission who was also receiving methotrexate; he presented with acute abdominal pain, fever, and sudden ascites one week after starting the drug, and a bone marrow aspiration showed no leukaemic activity. That single case does not establish a treatment.
Among 2165 liver transplant recipients at one centre between 2000 and 2015, the incidence of veno-occlusive disease was 0.3% (7 patients). Onset varied widely (median 4.7 months), and presentation combined liver failure and portal hypertension in variable degrees. Six of the seven patients had a preceding episode of acute cellular rejection. Two patients were treated by increasing immunosuppression plus interventional procedures (pleurodesis or transjugular intrahepatic portosystemic shunt), and two had successful retransplants. Three patients died (two from veno-occlusive disease, one from hepatocellular carcinoma recurrence). Five-year patient survival was 57.1%; five-year graft survival was 28.6%. A separate 2016 case report describes a 44-year-old woman who developed severe ascites and jaundice one month after liver transplant; veno-occlusive disease was diagnosed on clinical, pathologic, and radiologic grounds, she showed no response to medical therapy, and retransplant was the only remaining option.
What is still missing is a clear understanding of the pathogenesis, any proven pharmacologic prevention or treatment, and prospective data large enough to stratify patients by aetiology or severity. The available evidence consists of small retrospective series and single-case observations, with no controlled trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Oncology · 2000 · 63 citations
Veno-occlusive disease of the liver
AbstractThe success of high-dose cytoreductive strategies depends not only on antitumor activity but also on the tolerability of treatment. Although advances in supportive care have significantly reduced mortality due to infection and hemorrhage, regimen-related toxicities remain problematic. Hepatic veno-occlusive disease (VOD) is the most serious regimen-related toxicity after high-dose cytoreductive therapy. Risk factors for VOD are well established, but the biology of the syndrome remains poorly understood. Unfortunately, no pharmacologic approaches that clearly prevent or treat VOD have been identified. A better understanding of the pathogenesis of VOD will lead to more effective prevention and treatment strategies.
Reversible Hepatic Veno-Occlusive Disease and 6-Thioguanine
AbstractLetters and Corrections1 June 1982Reversible Hepatic Veno-Occlusive Disease and 6-ThioguanineN. KRIVOY, M.D., R. RAZ, M.D., A. CARTER, M.D., G. ALROY, M.D.N. KRIVOY, M.D.Search for more papers by this author, R. RAZ, M.D.Search for more papers by this author, A. CARTER, M.D.Search for more papers by this author, G. ALROY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-6-788_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with interest the article by Gill and associates (1). We report another case of reversible veno-occlusive disease of the liver caused by 6-thioguanine in a patient with acute leukemia in remission who was concomitantly treated with methotrexate.A 46-year-old man was hospitalized in April 1976 for evaluation of acute diffuse abdominal pain, fever, and sudden ascites that began 1 week before admission. In January 1976 he had been started on 6-thioguanine, 120 mg/d, and methotrexate, 30 mg/week. One week before hospitalization a bone marrow aspiration was done that did not show leukemic activity. At the...References1. GILLONSTADCARDAMONEMANEVALSUMNER RGJDH. Hepatic veno-occlusive disease caused by 6-thioguanine. Ann Intern Med. 1982;96:58-60. LinkGoogle Scholar2. BRAS G. Aspects of hepatic vascular lesions. In: GALL EA, MOSTOFI K, eds. The Liver. Baltimore: Williams & Wilkins Co.; 1973: 412-30. Google Scholar3. MEINDOKLANGER HB. Liver scan in Budd-Chiari syndrome. J Nucl Med. 1976;17:365-8. MedlineGoogle Scholar4. GRINEREL BADAWIPACKMAN PAH. Veno-occlusive disease after chemotherapy of acute leukemia. Ann Intern Med. 1976;85:578-82. LinkGoogle Scholar5. MITCHELLLAUTERBURG JB. Drug induced liver injury. Hosp Prac. 1978;13:95-106. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rambam Medical Center Haifa Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTioguanineOral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trialDRUGS USED IN CANCER CHEMOTHERAPYPurine Synthesis Inhibitors, 6-thioguanine and Azathioprine: Forgotten Treatment Options in Psoriasis and Psoriatic ArthritisA systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel diseaseToxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trialHepatotoxicity of ChemotherapyVascular Toxicity of Antineoplastic AgentsTioguaninePortal hypertension develops in a subset of children with standard risk acute lymphoblastic leukemia treated with oral 6-thioguanine during maintenance therapyEarly Hepatic Nodular Hyperplasia and Submicroscopic Fibrosis Associated With 6-Thioguanine Therapy in Inflammatory Bowel Disease6-Thioguanine can cause serious liver injury in inflammatory bowel disease patients.Early Nodular Hyperplasia of the Liver Occurring With Inflammatory Bowel Diseases in Association With Thioguanine TherapyVeno-occlusive disease in patients receiving thiopurines during maintenance therapy for childhood acute lymphoblastic leukaemiaHepatotoxicity Associated With 6-Thioguanine Therapy for Crohn's DiseaseHepatotoxicity of ChemotherapyANTIMETABOLITES AND CYTOTOXIC DRUGSVENO-OCCLUSIVE DISEASE OF THE LIVER ASSOCIATED WITH THIOPURINES IN A CHILD WITH ACUTE LYMPHOBLASTIC LEUKEMIACANCER CHEMOTHERAPY AND THE LIVERHEPATOTOXICITY OF CHEMOTHERAPEUTIC AND ONCOLOGIC AGENTS6-Thioguanine therapy for psoriasis causing toxic hepatic venoocclusive diseaseThioguanine used in maintenance therapy of chronic myeloid leukaemia causes non-cirrhotic portal hypertension. RESULTS FROM MRC CML II TRIAL COMPARING BUSULPHAN WITH BUSULPHAN AND THIOGUANINETREATMENT OF PSORIASIS WITH 6-THIOGUANINE12 Drug-induced vascular and sinusoidal lesions of the liverCytostatics and immunosuppressive drugs 1 June 1982Volume 96, Issue 6_Part_1Page: 788-788KeywordsAbdominal painAscitesBone marrowFeversHospitalizationsLiver diseasesMethotrexate Issue Published: 1 June 1982 PDF downloadLoading ...
Experimental and Clinical Transplantation · 2018 · 5 citations
Long-Term Outcome of Veno-Occlusive Disease After Liver Transplant: A Retrospective Single-Center Experience
AbstractOBJECTIVES: Veno-occlusive disease after liver transplant has been sporadically reported, and significant uncertainty exists concerning the best treatment and the long-term outcomes. Here, we reviewed our experience to evaluate clinical presentation, treatment, and the long-term outcomes of these patients. MATERIALS AND METHODS: Between 2000 and 2015, 2165 patients underwent liver transplant at our center. The incidence of veno-occlusive disease was 0.3% (7/2165). RESULTS: Timing of veno-occlusive disease onset (median 4.7 mo; interquartile range, 2.5-11.1 mo) varied widely as did clinical presentation, which was characterized by a variable association of liver failure and portal hypertension and different disease pro-gression rates. In all cases, diagnosis of veno-occlusive disease was confirmed by liver biopsy. Six patients (85.7%) presented with veno-occlusive disease after a previous episode of acute cellular rejection. Three patients died due to veno-occlusive disease (n = 2) or due to hepatocellular carcinoma recurrence (n = 1). Two patients were treated by increasing immunosuppression and with interventional procedures (pleurodesis and transjugular intrahepatic portosystemic shunt, respectively), and 2 had successful retransplants. 5-year patient and graft survival rates were 57.1% and 28.6%, respectively. CONCLUSIONS: A tailored approach based on clinical features and including retransplant can achieve acceptable long-term survival in patients with veno-occlusive disease after liver transplant.
Experimental and Clinical Transplantation · 2016 · 3 citations
Graft Failure From Hepatic Veno-Occlusive Disease After a Liver Transplant: A Case Report.
AbstractOBJECTIVES: Hepatic veno-occlusive disease after liver transplant is rare but potentially fatal. Here, we describe a case of veno-occlusive disease occurring after a liver transplant patient, which resulted in graft failure. CASE REPORT: A 44-year-old woman developed severe ascites accompanied with jaundice, for 1 month after a liver transplant that could not be explicated by common complications. Veno-occlusive disease was diagnosed basing on clinical, pathologic, and radiologic findings. The definitive pathogenesis was difficult to determine. The patient could not show any response to medical therapy, and her deteriorated clinical condition developed to hepatic failure, which called for retransplant. CONCLUSIONS: Veno-occlusive disease after a liver transplant can result in graft failure, and re-transplant may be the only alternative resource in critical case.
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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