DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cholestasis — screening already-approved drugs against its 19-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCholestasis maps to a 19-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
approvedUrsodeoxycholic acidApproved drug
Structures already discussed alongside cholestasis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of recombinant chicken liver Bile Acid Binding Protein (cL-BABP) — Ursodeoxycholic acid has a real, experimentally solved structure in complex with this target (PDB 9ETD, 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.
Loading structure…
helix sheet iu5drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9ETD · 2.3 Å · ligand Ursodeoxycholic acid (IU5). Experimental structure, not a prediction.
What the evidence adds up to
In a 2023 meta-analysis of 32 randomised controlled trials including 2153 children with cholestasis, ursodeoxycholic acid (UDCA) improved symptoms (risk ratio 1.24, 95% CI 1.18 to 1.29, moderate quality evidence) and reduced serum alanine aminotransferase, total bilirubin, direct bilirubin and total bile acid (low quality evidence). For specific subgroups, UDCA lowered aspartate aminotransferase in parenteral nutrition-associated cholestasis and γ-glutamyl transferase in infantile hepatitis syndrome and parenteral nutrition-associated cholestasis. Gastrointestinal adverse reactions occurred in 10.63% (67/630) of children on UDCA, but the incidence did not differ significantly from placebo or blank control (risk difference 0.03, 95% CI -0.01 to 0.06, moderate quality evidence) and did not vary with dose. The authors caution that long-term effects remain unexplored and recommend starting with a low dose.
Earlier reports describe the natural history and diagnostic challenges of cholestatic syndromes. A 1997 series of ten children with nonsyndromic paucity of interlobular bile ducts found that all presented with jaundice, seven had intermittent and three had persistent acholic stools, and five had pruritus. Liver biopsies showed intracellular cholestasis in all, portal fibrosis in four, and regenerative nodules in two. Fat-soluble vitamin deficiency complicated seven cases. Treatment included vitamin supplementation, cholestyramine, phenobarbital, prednisolone, or UDCA. One child received a successful liver transplant; three died. Consanguinity was 80% among parents, and five patients had affected siblings. A 2000 review of variant forms in adults notes that the most common chronic cholestatic liver diseases are primary biliary cirrhosis and primary sclerosing cholangitis, and that patients without the hallmarks of either are diagnosed by clinical and histological criteria: autoimmune cholangitis (AMA-negative, other autoantibodies present), small-duct PSC (inflammatory bowel disease with compatible biopsy but normal cholangiogram), or idiopathic adulthood ductopenia (ductopenia without PSC, inflammatory bowel disease, drug reaction, or sarcoidosis). A 2007 review of cholestatic syndromes highlights advances in understanding the farnesoid X receptor and sodium-dependent taurocholate cotransporting polypeptide, new insights into progressive familial intrahepatic cholestasis type 1, biliary atresia, intrahepatic cholestasis of pregnancy, and primary biliary cirrhosis, and important clinical trials in intrahepatic cholestasis of pregnancy, primary biliary cirrhosis, and primary sclerosing cholangitis, but concludes that much work remains.
What is still missing are large, long-term randomised trials in children and adults that stratify patients by specific cholestatic aetiology (e.g., biliary atresia, progressive familial intrahepatic cholestasis, primary sclerosing cholangitis) and that measure hard outcomes such as transplant-free survival rather than only biochemical improvements. Funding for such trials, particularly for rare paediatric cholestatic diseases, remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The American Journal of Gastroenterology · 2000 · 120 citations
Variant Forms of Cholestatic Diseases Involving Small Bile Ducts in Adults
AbstractOBJECTIVE: Cholestasis may result from diverse etiologies. We review chronic cholestatic disorders involving small intrahepatic bile ducts in the adult ambulatory care setting. Specifically, we discuss variant forms of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) as well as other conditions that may present diagnostic and therapeutic difficulties. METHODS: We conducted a MEDLINE search of the literature (1981-1997) and reviewed the experiences at the Mayo Clinic. All articles were selected that discussed antimitochondrial antibody (AMA)-negative PBC, small-duct PSC (formerly pericholangitis), and idiopathic adulthood ductopenia. RESULTS: The most common chronic cholestatic liver diseases affecting adults are PBC and PSC. Patients without the hallmarks of either syndrome are diagnosed according to their clinical and histological characteristics. Autoimmune cholangitis is diagnosed if clinical and histological features are compatible with PBC but autoantibodies other than AMA are present. Isolated small duct PSC is diagnosed if patients have inflammatory bowel disease, biopsy features compatible with PSC, but a normal cholangiogram. If ductopenia (absence of interlobular bile ducts in small portal tracts) is found histologically in the absence of PSC, inflammatory bowel disease, and other specific cholestatic syndromes such as drug reaction or sarcoidosis, the most likely diagnosis is idiopathic adulthood ductopenia. CONCLUSIONS: Based on these definitions, an algorithm for diagnosis and therapy in patients with laboratory evidence of chronic cholestasis may be constructed, pending results of further investigations into the etiopathogenesis of these syndromes.
Current Opinion in Gastroenterology · 2007 · 45 citations
Cholestasis and cholestatic syndromes
AbstractPURPOSE OF REVIEW: This review focuses on the recent advances in cholestatic liver diseases. While there is an emphasis placed on translational and treatment-focused studies, basic science studies with the greatest impact on the field are also covered. RECENT FINDINGS: Highlights include new discoveries for the role of the farsenoid X receptor and sodium-dependent taurocholate cotransporting polypeptide; new insights into the pathogenesis of progressive familial intrahepatic cholestasis type 1, biliary atresia, intrahepatic cholestasis of pregnancy, and primary biliary cirrhosis; new information for assessing prognosis in biliary atresia and primary biliary cirrhosis; and important clinical trials in intrahepatic cholestasis of pregnancy, primary biliary cirrhosis and primary sclerosing cholangitis. SUMMARY: The studies of 2006 have furthered our understanding of cholestasis and cholestatic syndromes. While we continue to add to our knowledge of pathogenesis and treatment for many of these diseases, much work remains.
Journal of Pediatric Gastroenterology and Nutrition · 1997 · 26 citations
Nonsyndromic Paucity of Interlobular Bile Ducts: Clinical and Laboratory Findings of 10 Cases
AbstractBACKGROUND: Reports concerning nonsyndromic paucity of the interlobular bile ducts are not common. METHODS: The clinical, biochemical, and histological features of ten such children were described. RESULTS: All presented with jaundice, starting in the first month in seven and in the fourth, seventeenth, and thirtieth month in the others. Alcoholic stools were present intermittently in seven and persistently in three patients. Pruritus was a prominent symptom in five. Liver function tests were abnormal in all but one. Liver biopsies were performed at ages of 20 days to 3 years (median 5 months). In addition to a paucity of interlobular bile ducts, histology revealed intracellular cholestasis in all, portal fibrosis in four, and regenerative nodules in two patients. Complications of fat-soluble vitamin deficiency occurred in seven. Therapy consisted of supplementation of those vitamins and administration of cholestyramine, phenobarbital, prednisolone, or ursodeoxycholic acid. While one child had a successful orthotopic liver transplantation, three died. Consanguinity rate was 80% among the parents, and five of the patients had siblings with similar symptoms. CONCLUSIONS: Prognosis of these patients is variable. Differentiation from other forms of cholestasis is important especially to avoid surgery.
Efficacy and safety of ursodeoxycholic acid in children with cholestasis: A systematic review and meta-analysis
AbstractOBJECTIVES: Ursodeoxycholic acid (UDCA) is the main therapeutic drug for cholestasis, but its use in children is controversial. We conducted this study to evaluate the efficacy and safety of ursodeoxycholic acid in children with cholestasis. METHODS: We searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, WanFang Data and VIP from the establishment of databases to July 2022. Eligible studies included Chinese or English randomized controlled trials (RCTs) comparing the efficacy and safety of no UDCA (placebo or blank control) and UDCA in children with cholestasis. This study had been registered with PROSPERO (CRD42022354052). RESULTS: A total of 32 RCTs proved eligible, which included 2153 patients. The results of meta-analysis showed that UDCA could improve symptoms of children with cholestasis (risk ratio 1.24, 95% CI 1.18 to 1.29; moderate quality of evidence), and serum levels of alanine aminotransferase, total bilirubin, direct bilirubin and total bile acid (low quality of evidence). For some children with specific cholestasis, UDCA could also effectively drop serum levels of aspartate aminotransferase (parenteral nutrition-associated cholestasis) and γ-glutamyl transferase (infantile hepatitis syndrome, parenteral nutrition-associated cholestasis). The most common adverse drug reactions (ADRs) of UDCA in children were gastrointestinal adverse reactions, with an incidence of 10.63% (67/630). There was no significant difference in the incidence of ADRs between UDCA and placebo/blank control groups (risk difference 0.03, 95%CI -0.01 to 0.06; moderate quality of evidence), and among children taking different UDCA doses (P = 0.27). CONCLUSION: The available short-term evidence showed that UDCA was effective and safe for children with cholestasis. Clinicians should use UDCA with caution (start with a low dose) until the long-term effect is further explored in future larger RCTs.
Revista médica de Chile · 2022 · 2 citations · open access
Colangitis biliar primaria: experiencia de cinco años en el Hospital Clínico de la Universidad de Chile
AbstractBACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease, which can progress to cirrhosis. It mainly affects middle-aged women. Its most frequent form of presentation is asymptomatic with biochemical cholestasis and the presence of antimitochondrial antibodies (AMA). AIM: To describe the epidemiological characteristics, clinical presentation and treatment for patients with PBC at a clinical hospital. MATERIAL AND METHODS: Descriptive, observational, retrospective study, carried out between January 2015 and December 2020. RESULTS: 179 patients (158 women) were cared in the study period. At the time of diagnosis, the median age was 54 years (range 24-76), 55% of them were asymptomatic, 45% had fatigue and 28% had pruritus. Positive AMA were present in 65% of patients, antinuclear antibodies (ANA) in 51%, and anti-smooth muscle antibodies (ASMA) in 9%. Immunoglobulin M (IgM) was elevated in 30% of the patients and 50% of patients were biopsied. Splenomegaly and esophageal varices were present in 24 and 22% of patients, respectively. PBC was associated with Sjogren's syndrome in 15%, hypothyroidism in 14%, osteoporosis in 13%, and scleroderma in 8%. CONCLUSIONS: The epidemiological characteristics of our patients agree with those published abroad. Laboratory cholestasis associated with the presence of AMA, currently allows diagnosis without the need for histological study. Ursodeoxycholic acid (UDCA) is the first-line treatment for patients with PBC. The use of biochemical response criteria is essential to identify patients who require other UDCA alternatives for isolated or combined treatment.
Effective Pharmacotherapy · 2019 · 1 citations · open access
Cholestasis (Cholestatic Hyperbilirubinemia) in Infants and Young Children: Definition, Causes, Differential Diagnosis, Conservative Therapy
AbstractCholestasis (cholestatic hyperbilirubinemia) in infants and young children refers to pathological state, the cause of which should be identi ed in the shortest possible time.e main causes of cholestasis development are hepatitis and biliary atresia.ey should be eliminated rst.When examining children with cholestasis, the most informative and accessible methods should be used.Cholestatis conservative therapy in this category of patients includes correction of nutrition, de ciency of fat-soluble vitamins and the use of choleretic drugs.
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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