{"id":"b6dda11b-5601-537c-9eae-a574ada86d40","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-wnt-tcf-blockade","predicate":"reduces","statement":"Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"0534a696-2977-5379-b763-feacce8fb903","mechanism_event_label":"Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.","subject":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"object":{"id":"3ce6566a-4713-506a-bd5d-a9bd67b6d5d8","slug":"wnt-tcf-target-expression","display_name":"WNT-TCF target gene expression","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0534a696-2977-5379-b763-feacce8fb903","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-wnt-tcf-blockade-event","event_type":"observed_relationship","label":"Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.","description":"Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.","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":"3ce6566a-4713-506a-bd5d-a9bd67b6d5d8","slug":"wnt-tcf-target-expression","display_name":"WNT-TCF target gene expression","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0b7e714b-d4b9-5ea1-ab3e-6dcc64e8d55c","slug":"ccnd1","display_name":"Cyclin D1 / CCND1","entity_type_key":"protein"},"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 cancer cell lines and xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ivermectin, with low-concentration effects rescued by direct activation with TCF-VP16","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In vivo inhibition was selective for TCF-dependent xenografts and absent in TCF-independent ones, which supports pathway specificity but does not establish the molecular binding partner.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human cancer cell lines and xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. (2014). https://pubmed.ncbi.nlm.nih.gov/25143352/ DOI: 10.15252/emmm.201404084","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":"Canonical WNT-TCF signalling output","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6a4e2948-6c73-5205-816a-e4281ef9806e","evidence_kind":"source_excerpt","locator":"Lines 200-209","start_line":200,"end_line":209,"excerpt":"## ivermectin-wnt-tcf-blockade\nIvermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.\nModel/species: Human cancer cell lines and xenografts\nTissue/system: Canonical WNT-TCF signalling output\nExposure: Ivermectin, with low-concentration effects rescued by direct activation with TCF-VP16\nRoute: In vitro and in vivo xenograft\nDuration: Not stated here\nLimits: In vivo inhibition was selective for TCF-dependent xenografts and absent in TCF-independent ones, which supports pathway specificity but does not establish the molecular binding partner.\nPrimary reference: The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. (2014). https://pubmed.ncbi.nlm.nih.gov/25143352/ DOI: 10.15252/emmm.201404084\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}