DeCure for Cholestasis, progressive familial intrahepatic, 4
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cholestasis, progressive familial intrahepatic, 4 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCholestasis, progressive familial intrahepatic, 4 maps to a 2-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 cholestasis, progressive familial intrahepatic, 4 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
ATP binding cassette subfamily B member 11 (ABCB11) — ABCB11 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8PMJ · 2.81 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Progressive familial intrahepatic cholestasis type 4 is not mentioned in any of the provided abstracts. The abstracts describe progressive familial intrahepatic cholestasis type 3 (PFIC-3), which is caused by mutations in the ABCB4 gene and inherited in an autosomal recessive pattern. About 200 patients with hepatobiliary disorders linked to ABCB4 mutations had been described in the literature by 2019. A 2024 case series reports two individuals from mainland Southeast Asia with a novel homozygous ABCB4 variant (c.779 T > C, p.L260P) and a clinical picture of cholestasis progressing to end-stage liver disease. PFIC-3 usually progresses to end-stage liver disease within the first two decades of life.
A 1981 report describes four siblings with familial intrahepatic cholestasis detected in early infancy. The two male siblings developed biliary cirrhosis and fatal hepatocellular carcinoma; the female siblings had persistent hepatomegaly and recurrent cholestasis. The authors note that the oncogenic risk, particularly in males, had not been generally appreciated. Benign recurrent intrahepatic cholestasis (BRIC), a separate condition, is described in a 1987 follow-up of one patient over 25 years with no adverse physical consequences or histological deterioration. A 2023 case series of three BRIC patients reports complete recovery after treatment with ursodeoxycholic acid and rifampicin, but the abstracts do not provide response rates, survival data, or sample sizes for any drug treatment in PFIC-4.
No abstract mentions a drug tested specifically for progressive familial intrahepatic cholestasis type 4. The 2023 BRIC series reports complete recovery with ursodeoxycholic acid and rifampicin, but BRIC is a distinct, self-limiting disorder, not PFIC-4. What is missing for PFIC-4 specifically is any published clinical trial, any identified genetic variant, any patient cohort with documented treatment outcomes, and any evidence that existing drugs alter the course of the disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Clinical Pathology · 1981 · 47 citations
Hepatoma in Siblings with Progressive Familial Cholestatic Cirrhosis of Childhood
AbstractThis report describes four siblings affected with familial intrahepatic cholestasis detected in early infancy. In the two male siblings, biliary cirrhosis and fatal hepatocellular carcinoma later developed, whereas the female siblings have had persistent hepatomegaly and recurrent episodes of cholestasis. Sequential biopsies show that this rare disorder of unknown etiology must be added to the many causes of giant cell transformation of the liver in infancy. Its oncogenic risk, particularly in males, has not been generally appreciated.
Postgraduate Medical Journal · 1987 · 16 citations · open access
Benign recurrent intrahepatic cholestasis--25 years of follow-up
AbstractOnly 70 cases of recurrent intrahepatic cholestasis have been reported in the literature since the original description of this entity in 1959. The benign nature of the disease has been questioned, some authors suggesting progression to biliary cirrhosis. We report our follow-up of one such patient for over 25 years with no adverse physical consequences or histological deterioration. Sequential liver biopsies were obtained during this period. A conservative approach to diagnosis and treatment is therefore indicated.
Indian Journal of Case Reports · 2023 · 0 citations · open access
Benign recurrent intrahepatic cholestasis – case series and literature review
AbstractBenign recurrent intrahepatic cholestasis (BRIC) is a rare form of intrahepatic cholestasis seen in patients with genetic predispositions. It is a rare disease of unknown prevalence and is transmitted as an autosomal recessive pattern of inheritance. The available literature for BRIC is limited. It is hard to formulate the true prevalence of the disorder. Often precipitated by a trigger like viral infections and drugs, this condition results in a self-limiting episode of cholestasis. We present a case series of three patients with the clinical picture of BRIC. All three cases were fully evaluated for the cause of cholestasis and thereafter treated with ursodeoxycholic acid and rifampicin, which showed complete recovery.
[Progressive familial intrahepatic cholestasis type 3].
AbstractProgressive familial intrahepatic cholestasis is caused by mutations in the ABCB4 gene and belongs to the family of familial intrahepatic cholestais disorders inherited in an autosomal recessive pattern. To date, about 200 patients with various hepatobiliary disorders associated with ABCB4 gene mutations have been described in the literature. The aim of this manuscript was to describe the pathogenesis, clinical presentation, diagnostic process and treatment of progressive familial intrahepatic cholestais type 3, based on the literature review.
A novel genetic variant associated with progressive familial intrahepatic cholestasis type 3: A case series
AbstractProgressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare disorder characterized by chronic cholestasis usually progressing to end-stage liver disease (ESLD) within the first two decades of life. PFIC-3 is caused by pathogenic genetic variants of the ATP-binding cassette 4 (ABCB4) gene with variable inheritance; the most common is autosomal recessive. We present two cases of PFIC-3 with genetic testing confirming a novel genetic variant in ABCB4 with homozygous genotype c.779 T > C, p.L260P. Both individuals are from mainland Southeast Asia and have a clinical picture consistent with cholestasis progressing to ESLD.
Greater South Information System · 2023 · 0 citations · open access
Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis
AbstractHereditary cholestatic liver disease caused by a class of autosomal gene mutations results in jaundice, which involves the abnormality of the synthesis, secretion, and other disorders of bile acids metabolism. Due to the existence of a variety of gene mutations, the clinical manifestations of children are also diverse. There is no unified standard for diagnosis and single detection method, which seriously hinders the development of clinical treatment. Therefore, the mutated genes of hereditary intrahepatic cholestasis were systematically described in this review.
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.
