Rare & Orphan Lab · DeCure for X

DeCure for Sclerosing cholangitis

DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for sclerosing cholangitis — screening already-approved drugs against its 43-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.

Disease module43 genesLead labRare & Orphan

All cures

Rare & OrphanDOID:14268$DeCureRare

The disease map

Disease moduleSclerosing cholangitis maps to a 43-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

ResearchComing soon

Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash

ValidationComing soon

In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report

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 sclerosing 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

C-C motif chemokine ligand 20 (CCL20) — CCL20 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 sindrag to rotate · scroll to zoom

RCSB Protein Data Bank · entry 7T1E · 1.459 Å · ligand SUCCINIC ACID (SIN). Experimental structure, not a prediction.

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 Drug Targets · 2016 · 0 citations

Current Targets for Primary Sclerosing Cholangitis

AbstractPrimary sclerosing cholangitis (PSC) is a biliary disease characterized by liver inflammation and death of cholangiocytes which, in turn, drive to fibrosis, cirrhosis and functional alterations of the liver. PSC is also associated with an increased risk of developing cholangiocarcinoma. To date, the etiopathogenesis of PSC is still not completely understood, although a genetic predisposition in association to environmental factors contribute to immune-mediated liver damage. The lack of such knowledge is responsible for the failure of most available therapies. At this time, many studies are evaluating potential approaches that could have a positive impact on the progression of the disease. This review aims to provide a summary of present and past therapeutic approaches for PSC.

https://doi.org/10.2174/1389450117666160112114152

Zeitschrift für Gastroenterologie · 2023 · 0 citations

The risk-variant rs56258221 at the BACH2-locus associates with skewed polarization of naive CD4+T cells towards pro-inflammatory phenotypes in primary sclerosing cholangitis

AbstractBackground and Aims The pathogenesis of Primary sclerosing cholangitis (PSC) is still unknown. Intrahepatic naive-like T cell population prone to polarize towards TH17 phenotype and several polymorphisms in immune-related genes has been linked to PSC. We hypothesized that genetic predisposition contributing to T cell phenotype in patients with PSC. Methods Patients with PSC (n=270) were genotyped for the disease-associated risk variants rs56258221 (BACH2), rs80060485 (FOXP1), rs4147359 (IL2RA) and rs7426056 (CD28). T cell function and phenotype, in vitro polarization and proliferation, microRNA-assays, western blots and single-cell RNA sequencing was performed. Results Functional in vitro experiments with naive CD4+T cells from patients with PSC and healthy donors (HD) as controls showed increased capacity of PSC-derived cells to convert into pro-inflammatory T Helper 1 (TH1, 50.7% vs. 42.9%, p=0.027) and T Helper 17 (TH17, 5,5% vs. 2,2%, p=0.042) subsets. Moreover, lower conversion rate into induced regulatory T cells (iTREG, 9.6% vs. 17.3%, p=0.022) could be detected. The observed effects were increased in rs56258221 (BACH2) carriers and not seen for the other variants in immune-related genes assessed. Interestingly, single-cell RNA sequencing of the T cell compartment identified a composition skewed towards activated phenotypes in rs56258221-carriers.Reduction of BACH2 on protein level was linked to a strongly increased expression of microRNA 4464, previously imputed to inhibit translation of BACH2. Conclusion We here present comprehensive data linking the risk variant rs56258221 to the recently described dysregulated T cell phenotype in patients with PSC. Publication History Article published online: 18 January 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

https://doi.org/10.1055/s-0042-1760065

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.

Research recordComing soon

Budgets appear when the experiment is real

A campaign opens only with a defined candidate, an assay scope and decision rule, a qualified research organization, a real budget and a publication plan. Funding then moves by evidence milestones.

Methods, raw data and analysis are released as an open research package.

$DECURE carries no equity, royalty or claim on a paper, patent or laboratory.

A well-executed negative result closes a path and improves the next decision. It counts.

A computational result earns attention. Only experimental evidence earns confidence.

Research stages and campaign status are published as they change.

The method, with the number0.60

DeepOracle — network proximity + signature reversal

0.60

external AUROC on repoDB (approved vs failed) · CI₉₅ 0.578–0.622

2,708

independent drug–disease pairs across 455 diseases

0.50

label-shuffle control — collapses to chance, so the signal is not leakage

The score is computed only by the oracle. No language model ever writes it.

Open data only — Open Targets 26.03 · ChEMBL · STRING v12.

In-silico prioritization, not proof of efficacy. Every candidate is a hypothesis for a human expert to validate in the wet-lab.

Who works on this disease6

Patient organisations & advocacy

Research centres running trials · 100+ studies on ClinicalTrials.gov

Mayo Clinic10 trials
Perspectum5 trials
Gilead Sciences4 trials
Assistance Publique - Hôpitaux de Paris4 trials
Stanford University4 trials
Mirum Pharmaceuticals, Inc.3 trials

Independent organisations and research centres working on this disease. Listed for patients and researchers — no affiliation with DeCure is claimed or implied.