{"id":"9b0031ad-a426-5721-9668-464bface4022","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-leukemia-reactive-oxygen","predicate":"increases","statement":"Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"807722ce-ca3d-59a2-9f2f-3ae872141cb0","mechanism_event_label":"Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.","subject":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"object":{"id":"b51f3150-efc0-5413-a47a-01d094d248b7","slug":"reactive-oxygen-species","display_name":"Reactive oxygen species","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"807722ce-ca3d-59a2-9f2f-3ae872141cb0","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-leukemia-reactive-oxygen-event","event_type":"observed_relationship","label":"Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.","description":"Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.","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":"b51f3150-efc0-5413-a47a-01d094d248b7","slug":"reactive-oxygen-species","display_name":"Reactive oxygen species","entity_type_key":"chemical_species"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8be23eb0-6c40-5646-bdac-b802a442b9d9","slug":"leukemia-intracellular-chloride","display_name":"Intracellular chloride concentration in leukemia cells","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not stated here","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":"Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Low micromolar ivermectin; mouse dosing described as appearing pharmacologically achievable","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Death was preferential for leukemia cells over normal hematopoietic cells rather than exclusive to them, and synergy was reported with cytarabine and daunorubicin, which also raise reactive oxygen species.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro and in vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Reactive oxygen species and cell viability","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"58168003-98ab-5bdb-bec0-a8464a5306e1","evidence_kind":"source_excerpt","locator":"Lines 189-198","start_line":189,"end_line":198,"excerpt":"## ivermectin-leukemia-reactive-oxygen\nIvermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.\nModel/species: Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models\nTissue/system: Reactive oxygen species and cell viability\nExposure: Low micromolar ivermectin; mouse dosing described as appearing pharmacologically achievable\nRoute: In vitro and in vivo\nDuration: Not stated here\nLimits: Death was preferential for leukemia cells over normal hematopoietic cells rather than exclusive to them, and synergy was reported with cytarabine and daunorubicin, which also raise reactive oxygen species.\nPrimary reference: The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675\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}