{"id":"38f7118b-ae93-56e8-8577-9b78b0e59f89","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-pak1-akt-autophagy","predicate":"reduces","statement":"Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c13f149a-551a-5823-a865-9e9ab305bbc2","mechanism_event_label":"Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.","subject":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"object":{"id":"dab8b230-da39-5a24-aaed-f9465c65b96e","slug":"pak1","display_name":"P21-activated kinase 1 / PAK1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"c13f149a-551a-5823-a865-9e9ab305bbc2","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-pak1-akt-autophagy-event","event_type":"observed_relationship","label":"Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.","description":"Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.","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":"dab8b230-da39-5a24-aaed-f9465c65b96e","slug":"pak1","display_name":"P21-activated kinase 1 / PAK1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"96c440c0-9a81-57cb-a09a-3e06dd6c3e84","slug":"breast-cancer-cytostatic-autophagy","display_name":"Cytostatic autophagy in breast cancer 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":"Human breast cancer cells and breast cancer xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ivermectin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The autophagy described is cytostatic and associated with suppressed tumour growth rather than cytotoxic killing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human breast cancer cells and breast cancer xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. (2016). https://pubmed.ncbi.nlm.nih.gov/27302166/ DOI: 10.1158/0008-5472.CAN-15-2887","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro and in vivo xenograft","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"PAK1 abundance, Akt phosphorylation and autophagy","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"38589a1f-acd5-5bc8-acd8-eb7634a2bba4","evidence_kind":"source_excerpt","locator":"Lines 211-220","start_line":211,"end_line":220,"excerpt":"## ivermectin-pak1-akt-autophagy\nIvermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.\nModel/species: Human breast cancer cells and breast cancer xenografts\nTissue/system: PAK1 abundance, Akt phosphorylation and autophagy\nExposure: Ivermectin\nRoute: In vitro and in vivo xenograft\nDuration: Not stated here\nLimits: The autophagy described is cytostatic and associated with suppressed tumour growth rather than cytotoxic killing.\nPrimary reference: Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. (2016). https://pubmed.ncbi.nlm.nih.gov/27302166/ DOI: 10.1158/0008-5472.CAN-15-2887\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. 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