{"id":"35caf7ef-1c03-5f10-87a2-23a7557a3699","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-fxr-ligand","predicate":"activates","statement":"Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"a90abff5-594e-569c-a6bb-1fad84cb6eeb","mechanism_event_label":"Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.","subject":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"object":{"id":"fcb53473-c0bd-5e70-891f-ab3b48353d25","slug":"nr1h4","display_name":"Human farnesoid X receptor / NR1H4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"a90abff5-594e-569c-a6bb-1fad84cb6eeb","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-fxr-ligand-event","event_type":"observed_relationship","label":"Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.","description":"Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fcb53473-c0bd-5e70-891f-ab3b48353d25","slug":"nr1h4","display_name":"Human farnesoid X receptor / NR1H4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not applicable","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"High-throughput compound library screen, FXR ligand-binding domain crystal structure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ivermectin complexed with the FXR ligand-binding domain","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The authors describe FXR as the first mammalian protein targeted by ivermectin with high selectivity, which is a claim about selectivity among mammalian targets rather than about potency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"High-throughput compound library screen, FXR ligand-binding domain crystal structure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro and structural","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Nuclear receptor transcriptional activity and coregulator recruitment","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"79cb0e86-cc2a-591b-901b-5ab2b058cc13","evidence_kind":"source_excerpt","locator":"Lines 123-132","start_line":123,"end_line":132,"excerpt":"## ivermectin-fxr-ligand\nIvermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.\nModel/species: High-throughput compound library screen, FXR ligand-binding domain crystal structure\nTissue/system: Nuclear receptor transcriptional activity and coregulator recruitment\nExposure: Ivermectin complexed with the FXR ligand-binding domain\nRoute: In vitro and structural\nDuration: Not applicable\nLimits: The authors describe FXR as the first mammalian protein targeted by ivermectin with high selectivity, which is a claim about selectivity among mammalian targets rather than about potency.\nPrimary reference: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"20818ddd-7b37-5226-a24b-7de007e80eb2","stable_key":"import-e0801c92-7fd3-5cb2-82b7-dd82f010f3ed","title":"Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"c7e1e0201cbd222f0c52b7981f078936ed39b617d747821ed6daa584c2b964a7","revision_id":"56746c3e-cdec-5b8f-a191-425de1a0a7ce","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}