DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for bile acid conjugation defect 1 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBile acid conjugation defect 1 maps to a 1-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 bile acid conjugation defect 1 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.
What the evidence adds up to
The abstracts provided do not describe bile acid conjugation defect 1. They cover atrial fibrillation risk, bile acid diarrhoea management, gallstone dissolution with ursodeoxycholic acid, sulfonamide drug concentrations in bile, and sodium benzoate plus taurocholic acid feeding in post-surgical patients. No patient with bile acid conjugation defect 1 appears in any of these studies.
In the 1982 gallstone study, 7 of 10 patients showed stone dissolution after ursodeoxycholic acid treatment. The glycine-to-taurine conjugated bile acid ratio rose significantly after treatment (p < 0.001 versus pre-treatment, p < 0.005 versus control). The 1975 sodium benzoate and taurocholic acid feeding experiment found no change in glycine-conjugated bile acid output with sodium benzoate alone; adding taurocholic acid increased total and taurine-conjugated bile acid output and reduced the glycine-to-taurine ratio, but the authors concluded the combination offered no benefit over taurocholic acid alone.
The 2024 review on bile acid diarrhoea notes that bile acid sequestrants remain the main drugs used, with better-quality data now available for colesevelam. It also mentions that the GLP-1 receptor agonist liraglutide is effective, though mechanisms are unclear, and that FXR agonists require further validation. The 2015 metabolomics study found that higher levels of two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were associated with increased atrial fibrillation risk in African Americans, with hazard ratios of 1.22 per standard deviation for each.
What is missing for bile acid conjugation defect 1 specifically: no abstract addresses this disease. There are no data on any drug tested in patients with this condition, no trial design, no patient stratification, and no funding directed at this disorder in the provided literature.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2015 · 43 citations · open access
Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study
AbstractBACKGROUND: Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited. METHODS: We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987-1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates. RESULTS: During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12-1.32) for glycolithocholate sulfate and 1.22 (1.10-1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes. CONCLUSION: We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted.
Expert Review of Gastroenterology & Hepatology · 2024 · 11 citations · open access
Managing bile acid diarrhea: aspects of contention
AbstractINTRODUCTION: Bile acid diarrhea is a common cause of bowel symptoms and often goes unrecognized or misdiagnosed. Many aspects of management remain contentious. AREAS COVERED: The primary, idiopathic condition should be suspected in people with functional diarrhea or diarrhea-predominant irritable bowel syndrome. Secondary causes include ileal resection, inflammation, and post-cholecystectomy. Diagnostic tests vary globally, being unavailable in many countries, and further refinement of testing strategy is needed. Management is usually long-term symptom control, rather than reversal of the causative factors, which are still being defined. Bile acid sequestrants remain the main drugs used. They are relatively inexpensive, and better-quality data is now available for colesevelam. However, optimal use, including timing and formulation, needs clarification. The GLP-1 receptor agonist, liraglutide, is also effective, although mechanisms of action and whether this effect is common to other class members is unclear. They are more expensive, and availability varies. FXR agonists can also be effective but require further validation. The role of dietary factors in symptom development is a major patient concern, needing more formal studies. EXPERT OPINION: To build on recent findings, bile acid diarrhea needs further investment into causes, diagnosis and therapy to guide present and future patient care.
The Tohoku Journal of Experimental Medicine · 1982 · 7 citations · open access
The effect of ursodeoxycholic acid on biliary bile acid composition in patients with cholesterol gallstone.
AbstractTo elucidate the role of conjugated biliary bile acids in gallstone dissolution, the acids in bile were determined by high-performance liquid chromatography before and after the treatment with ursodeoxycholic acid for 3-26 months in patients with gallstone. The stone-dissolving effect of ursodeoxycholic acid was confirmed in 7 of 10 patients and the lithogenic index lowered significantly after the treatment. The compositions of cholate, chenodeoxycholate and ursodeoxycholate were about 33, 45 and 4%, respectively, in the control and pre-treatment groups. In the post-treatment group, a markedly low value was observed in primary bile acids both glycine-conjugates and taurine-conjugates, especially in cholate, with a significantly high value of ursodeoxycholate (p less than 0.001) of both conjugates. On the other hand, no difference was observed in the composition of deoxycholate with significantly low percentage of taurine-conjugates compared with that in the pre-treatment group. The ratio of glycine- to taurine-conjugated bile acids showed a significantly higher value in the post-treatment group than in the pre-treatment group (p less than 0.001) and the control group (p less than 0.005). The bile specimens were measured concomitantly by gas-liquid chromatography and the results were compared with those of high-performance liquid chromatography. The mean value of total bile acids, the ratio of cholate to chenodeoxycholate and the ratio of glycine- to taurine-conjugated bile acids obtained by the former analysis procedure represented about 57, 80 and 115% of those of the latter. It is concluded that the high G/T value seems to have a role in the dissolution mechanism.
Experimental Biology and Medicine · 1941 · 4 citations · open access
Concentration of Free Sulfanilamide, Sulfapyridine and Sulfathiazol in Material Drained from Human Biliary Tract
AbstractTwo grams of sulfanilamide, sulfapyridine and sulfathiazol were ingested in successive experiments by 4 patients from whom bile was draining through tubes inserted in the bile duct after operations upon the biliary tract. Intervals of 3 or 4 days separated the experiments upon each subject. A satisfactory test with sulfapyridine was not obtained in one instance. Specimens of bile were collected for 4 successive 4-hour periods in each experiment. The first period preceded, and the others followed the ingestion of the drug. Samples of urine were collected simultaneously with the bile specimens after the drug had been given, and a sample of blood was drawn at the midpoint of each of these 3 4-hour periods. The free compounds were determined in the specimens of bile by the diazo technic of Bratton and Marshall in the presence of acetone. Since the usual methods for clarifying solutions, including the one used upon bile by Hubbard and Anderson precipitated a rather high proportion of added sulfathiazol, the bile was clarified by the use of 2 successive precipitations with barium—first in alkaline solution as the phosphotungstate and then in acid solution as the sulfate. The sulfonamide drugs could be determined with an accuracy of about 5%, or, if present in very low concentrations, to the nearest 0.1 mg per 100 cc by this procedure. Control specimens, analyzed as a part of each experiment, gave no red color by the technic. The concentrations of the drugs in the urine were determined after dilution, one part to 100, by the same diazo technic. Blood analyses were carried out as described by Bratton and Marshall. The results upon the blood and bile of different subjects were qualitatively similar, except for such variations in actual blood concentrations as would be expected from the varying ease of absorption of the different compounds studied.
Experimental Biology and Medicine · 1975 · 2 citations
The Effect of Sodium Benzoate and Taurocholic Acid Feeding on Human Bile Composition
AbstractFour patients were fed sodium benzoate after stabilization following common bile duct exploration. Bile collections revealed no change in the output of glycine conjugated bile acids. Three patients had taurocholic acid added to the regimen after 3 days and demonstrated a significant increase in total and taurine conjugated bile acid output with marked reduction of the G/T ratio. These latter changes are similar to those produced by taurocholic acid feeding alone and therefore no benefit of the combination of drugs on bile salt excretion or conjugation ratio was demonstrated.
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.
