DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cholangitis — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCholangitis maps to a 3-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 cholangitis 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
nuclear receptor subfamily 1 group H member 4 (NR1H4) — NR1H4 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 iiidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3BEJ · 1.9 Å · ligand YTTRIUM (III) ION (YT3). Experimental structure, not a prediction.
What the evidence adds up to
One randomised trial of D-penicillamine versus placebo in 70 patients with primary sclerosing cholangitis found no significant effect on mortality (relative risk 1.14, 95% CI 0.49 to 2.64), liver transplantation (RR 1.11, 95% CI 0.39 to 3.17), hepatic histologic progression (RR 1.17, 95% CI 0.79 to 1.74), or cholangiographic deterioration (RR 0.87, 95% CI 0.43 to 1.79). Serum aspartate aminotransferase improved (weighted mean difference -23.00 U/L; 95% CI -30.66 to -15.34), but serum bilirubin and alkaline phosphatase did not. Adverse events were significantly more frequent with D-penicillamine (P = 0.013). The trial was of low methodological quality, and the Cochrane review authors do not recommend the drug outside randomised trials.
For primary biliary cholangitis, a 2020 review notes that a large percentage of patients have incomplete response or intolerance to the two currently approved treatments. New drugs targeting bile-acid regulation, immune-modulation, and fibrogenic pathways are in early development. PPAR agonists, FGF19 analogs, and FXR agonists are described as promising agents based on early results, but no phase III data or concrete response rates from these investigational drugs are provided in the abstract. A 2023 Chinese technical guideline for clinical trials of drugs for primary biliary cholangitis was issued to standardise trial design, focusing on selection of test populations and efficacy endpoints, reflecting the limited drug options and active clinical development.
An article on acute cholangitis states that modern diagnostic and therapeutic modalities have greatly decreased mortality, but gives no specific numbers or drug names.
What is still missing: for primary sclerosing cholangitis, no adequately powered, high-quality randomised trial of any drug has shown improved survival or reduced need for transplantation. For primary biliary cholangitis, the investigational drugs lack published phase III results with hard endpoints; the field needs trials that stratify patients by biochemical response and histologic stage, and funding for long-term outcome studies rather than surrogate markers alone.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cochrane Database of Systematic Reviews · 2006 · 13 citations · open access
D-penicillamine for primary sclerosing cholangitis
AbstractBACKGROUND: Primary sclerosing cholangitis is a cholestatic disease. D-penicillamine is suggested as a treatment option due to its copper reducing and immunomodulatory potential. OBJECTIVES: To evaluate the beneficial and harmful effects of D-penicillamine for patients with primary sclerosing cholangitis. SEARCH STRATEGY: Eligible trials were identified through searches of The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 3, 2005), MEDLINE (1950 to August 2005), EMBASE (1980 to August 2005), Science Citation Index EXPANDED (1945 to August 2005), and reference lists of relevant articles. Authors of trials and pharmaceutical companies known to produce D-penicillamine were also contacted. SELECTION CRITERIA: Randomised clinical trials comparing D-penicillamine in any dose, duration, and route of administration versus placebo, no intervention, or other intervention(s). Trials were included irrespective of publication status, year of publication, language, or blinding. DATA COLLECTION AND ANALYSIS: Both authors selected the trials, extracted data, and evaluated the methodological quality of the trials with respect to the generation of allocation sequence, allocation concealment, blinding, and follow-up. The results were reported by intention-to-treat analysis. The outcomes were presented as relative risk (RR) or weighted mean difference (WMD), both with 95% confidence intervals (CI). MAIN RESULTS: One randomised trial was identified and included in the review. It was of low methodological quality. The trial compared D-penicillamine versus placebo in 70 patients with primary sclerosing cholangitis. Compared with placebo, D-penicillamine therapy had no significant effect on mortality (RR 1.14, 95% CI 0.49 to 2.64), liver transplantation (RR 1.11, 95% CI 0.39 to 3.17), hepatic histologic progression (RR 1.17, 95% CI 0.79 to 1.74), or cholangiographic deterioration (RR 0.87, 95% CI 0.43 to 1.79). D-penicillamine led to a significant improvement in the serum aspartate aminotransferase (WMD -23.00 U/L; 95% CI -30.66 to -15.34), but not in serum bilirubin level (WMD 0.40 mg/L; 95% CI -0.19 to 0.99) and serum alkaline phosphatases activity (WMD 44.00 U/L; 95% CI -37.89 to 125.89). There were significantly more adverse events in patients receiving D-penicillamine (P = 0.013). AUTHORS' CONCLUSIONS: There is not sufficient evidence to support or refute the use of D-penicillamine for patients with primary sclerosing cholangitis. We do not recommend the use of D-penicillamine for patients with primary sclerosing cholangitis outside randomised trials.
Expert Opinion on Investigational Drugs · 2020 · 8 citations
Investigational drugs in early phase development for primary biliary cholangitis
AbstractIntroduction: With a large percentage of patients having an incomplete response or intolerance to current FDA approved medications, new therapies for the treatment of primary biliary cholangitis are in great demand.Areas covered: In this review, we assess currently available drugs as well as promising new therapies for the treatment of primary biliary cholangitis. A literature search was performed with the following search terms: ‘PBC treatment,’ ‘PBC therapeutics,’ ‘PBC clinical trials,’ and included original articles, meta-analyses, and systematic reviews from 1 January 1981, to 1 January 2020. ClinicalTrials.gov was accessed for data from ongoing trials.Expert opinion: Targeted drug therapies offer an alternative for patients who are unable to meet their therapeutic goals with either of the two currently approved treatment options. Specifically, new drugs targeting bile-acid regulation, immune-modulation, and fibrogenic pathways are currently in development with multiple agents showing encouraging early results with the ultimate goal of developing therapies that will achieve high rates of biochemical remission, will be well tolerated, and improve symptoms and quality of life in patients with primary biliary cholangitis. Based on a review of the current literature, PPAR agonists appear to be promising agents, along with FGF19 analogs and FXR agonists.
Developpement du >: une asymetrie entre filles et garcons?
AbstractAcute cholangitis remains a potentially lethal disease if not appropriately diagnosed in a timely fashion. Modern diagnostic and therapeutic modalities have greatly decreased mortality from acute cholangitis. This article aims to provide an up-to-date synopsis of empirically tested diagnostic criteria as well as an overview of the expanding interventions available.
[Interpretation of key points of the technical guidelines for clinical trials of drugs for the treatment of primary biliary cholangitis].
AbstractThere are limited drug options in the field of primary biliary cholangitis, so there is a great clinical need. In recent years, research and development of PBC treatment medications have been active domestically and internationally, and clinical trials have been conducted on multiple drugs with distinct targets. Therefore, on February 13, 2023, the State Drug Administration issued the "Technical Guidelines for Clinical Trials of Drugs for the Treatment of Primary Biliary Cholangitis" in order to guide and standardize the clinical trials of drugs for the treatment of PBC. This article briefly summarizes the key points of the guiding principles, focuses on the difficulties of clinical evaluation of drugs, discusses the key elements of clinical trials such as the selection of test populations and efficacy endpoints, and introduces the determination process through literature searches and expert discussion methods combined with reviewer experience and scientific considerations.
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.
