{"doi":"10.1002/advs.202508751","title":"AI‐Assisted Drug Re‐Purposing for Human Liver Fibrosis","abstract":"Liver fibrosis has few treatment options due to the poor quality of the available animal and in vitro models. To address this, a hypothesis generating multi-agent AI system (AI co-scientist) is used to assist in re-purposing drugs for treatment of liver fibrosis and direct their experimental characterization. The anti-fibrotic efficacy and toxicity of 25 drugs are serially assessed in multi-lineage human hepatic organoids grown in microwells (i.e., microHOs). Remarkably, three previously characterized anti-fibrotic drugs and two AI co-scientist-recommended drugs that targeted epigenomic modifiers exhibited significant anti-fibrotic activity and they promoted liver regeneration. Analysis of these five anti-fibrotic drugs revealed that they all can reduce the generation of activated myofibroblasts and that each drug have unique effects on mesenchymal cells that generated their anti-fibrotic effects. Since all five of the anti-fibrotic drugs reduced TGFβ-induced chromatin structural changes, epigenomic changes play an important role in the pathogenesis of liver fibrosis. One AI co-scientist recommended drug is an FDA-approved anti-cancer treatment (Vorinostat) that reduced TGFβ-induced chromatin structural changes by 91% and promoted liver parenchymal cell regeneration in microHOs. Hence, the integrated use of AI co-scientist and this microHO platform identified a potential new generation of liver fibrosis treatments that also promote liver regeneration.","journal":"Advanced Science","year":2025,"id":514916,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273514,"name":"Lu Cui","orcid":"0000-0002-3531-8102","position":1,"is_corresponding":false},{"id":1378347,"name":"Jakkapong Inchai","orcid":"0000-0002-9725-9611","position":2,"is_corresponding":false},{"id":555731,"name":"Zhuoqing Fang","orcid":"0000-0002-7418-1313","position":3,"is_corresponding":false},{"id":1378348,"name":"James Law","orcid":"0000-0002-1608-8970","position":4,"is_corresponding":false},{"id":1378964,"name":"Alberto Alonzo Garcia Brito","orcid":null,"position":5,"is_corresponding":false},{"id":830230,"name":"Annalisa Pawlosky","orcid":"0000-0003-3408-986X","position":6,"is_corresponding":false},{"id":1362042,"name":"Juraj Gottweis","orcid":null,"position":7,"is_corresponding":false},{"id":1378965,"name":"Alexander Daryin","orcid":null,"position":8,"is_corresponding":false},{"id":1378966,"name":"Anatoly Myaskovsky","orcid":null,"position":9,"is_corresponding":false},{"id":1124318,"name":"Lakshmy Ramakrishnan","orcid":"0000-0002-8582-3705","position":10,"is_corresponding":false},{"id":1163100,"name":"Anil Palepu","orcid":null,"position":11,"is_corresponding":false},{"id":1378349,"name":"Kavita Kulkarni","orcid":"0000-0003-3089-3623","position":12,"is_corresponding":false},{"id":573881,"name":"Wei‐Hung Weng","orcid":"0000-0003-2232-0390","position":13,"is_corresponding":false},{"id":1011985,"name":"Zhuanfen Cheng","orcid":null,"position":14,"is_corresponding":false},{"id":1201685,"name":"Vivek Natarajan","orcid":"0000-0001-7849-2074","position":15,"is_corresponding":false},{"id":1201676,"name":"Alan Karthikesalingam","orcid":"0009-0000-4958-5976","position":16,"is_corresponding":false},{"id":1378967,"name":"Keran Rong","orcid":null,"position":17,"is_corresponding":false},{"id":1378350,"name":"Yunhan Xu","orcid":"0000-0001-5315-9160","position":18,"is_corresponding":false},{"id":1378351,"name":"Tao Tu","orcid":"0000-0001-5508-4369","position":19,"is_corresponding":false},{"id":555735,"name":"Gary Peltz","orcid":"0000-0001-6191-7697","position":20,"is_corresponding":false},{"id":555730,"name":"Yuan Guan","orcid":"0000-0001-7506-1893","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:48:34.431522Z","pmid":"40946179","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}