{"id":"0dca1f56-4b85-5239-b16a-4f8d7d2ab07b","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-glucl-open-pore","predicate":"stabilizes_open_state_of","statement":"Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"1adb9a46-baa7-5b3d-bb43-88aa865522db","mechanism_event_label":"Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.","subject":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"object":{"id":"fc88a4d0-ca7b-5010-9741-8ea62d0894f3","slug":"celegans-glucl","display_name":"Caenorhabditis elegans glutamate-gated chloride channel alpha / GluCl","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1adb9a46-baa7-5b3d-bb43-88aa865522db","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-glucl-open-pore-event","event_type":"observed_relationship","label":"Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.","description":"Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.","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":"fc88a4d0-ca7b-5010-9741-8ea62d0894f3","slug":"celegans-glucl","display_name":"Caenorhabditis elegans glutamate-gated chloride channel alpha / GluCl","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":"Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"GluCl-Fab complex determined with ivermectin as allosteric agonist, and separately with L-glutamate and picrotoxin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A structure establishes a binding site and a stabilised conformation; it does not establish the concentration at which this occurs in a living parasite.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Principles of activation and permeation in an anion-selective Cys-loop receptor. (2011). https://pubmed.ncbi.nlm.nih.gov/21572436/ DOI: 10.1038/nature10139","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Structural","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Anion-selective Cys-loop receptor gating and permeation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b7054bca-9e32-58d6-9380-d0631a7645b7","evidence_kind":"source_excerpt","locator":"Lines 24-33","start_line":24,"end_line":33,"excerpt":"## ivermectin-glucl-open-pore\nIvermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.\nModel/species: Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution\nTissue/system: Anion-selective Cys-loop receptor gating and permeation\nExposure: GluCl-Fab complex determined with ivermectin as allosteric agonist, and separately with L-glutamate and picrotoxin\nRoute: Structural\nDuration: Not applicable\nLimits: A structure establishes a binding site and a stabilised conformation; it does not establish the concentration at which this occurs in a living parasite.\nPrimary reference: Principles of activation and permeation in an anion-selective Cys-loop receptor. (2011). https://pubmed.ncbi.nlm.nih.gov/21572436/ DOI: 10.1038/nature10139\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}