{"id":"fa52c11c-be57-543f-a9d1-dace24bb48cf","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-silychristin-mct8","predicate":"inhibits","statement":"Silychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"a4ba1db3-6de1-542f-897f-3a781d4df65e","mechanism_event_label":"An experimental inhibitor can block hormone passage through MCT8.","subject":{"id":"1577c4d6-6612-55c5-84f5-e63a776d944a","slug":"silychristin","display_name":"Silychristin","entity_type_key":"small_molecule"},"object":{"id":"a146600b-de7a-56b1-9ae1-8a51e4f053b2","slug":"cellular-thyroxine-uptake","display_name":"Cellular thyroxine uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a4ba1db3-6de1-542f-897f-3a781d4df65e","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-silychristin-mct8-event","event_type":"biochemical_relationship","label":"An experimental inhibitor can block hormone passage through MCT8.","description":"Silychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1577c4d6-6612-55c5-84f5-e63a776d944a","slug":"silychristin","display_name":"Silychristin","entity_type_key":"small_molecule"},"role":"inhibitor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"98c25617-10b5-50ab-b330-7e6b7fa595bb","slug":"slc16a2","display_name":"Human MCT8 / SLC16A2","entity_type_key":"protein"},"role":"transporter","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f2b25f38-ec94-57d0-a46d-dd0fee45f01e","slug":"thyroxine","display_name":"T4","entity_type_key":"small_molecule"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a146600b-de7a-56b1-9ae1-8a51e4f053b2","slug":"cellular-thyroxine-uptake","display_name":"Cellular thyroxine uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_locator","value_text":"Figures 1a-b and 4; Results: inhibitor mechanism","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/iodine-metabolism-sources/40368961.txt\", \"locator\": \"Figures 1a-b and 4; Results: inhibitor mechanism\", \"start_char\": 17453, \"end_char\": 22253}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cell assays used 10 micromolar T4 with or without 10 micromolar silychristin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Drug-compound experiment; does not establish dietary milk-thistle effects or an iodine-supplement interaction at usual exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An experimental inhibitor can block hormone passage through MCT8.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HeLa cells and purified MCT8","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"45bcff16-ec45-5616-ade2-4936c5019857","evidence_kind":"source_excerpt","locator":"Lines 926-938","start_line":926,"end_line":938,"excerpt":"### i-met-silychristin-mct8\nSilychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An experimental inhibitor can block hormone passage through MCT8.\norganism: Human\ntissue_or_cell_type: HeLa cells and purified MCT8\nexperimental_model: Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays\nlimitations: Drug-compound experiment; does not establish dietary milk-thistle effects or an iodine-supplement interaction at usual exposure.\nexposure: Cell assays used 10 micromolar T4 with or without 10 micromolar silychristin.\nevidence_locator: Figures 1a-b and 4; Results: inhibitor mechanism\nevidence_spans: [{\"source_document\": \"artifacts/iodine-metabolism-sources/40368961.txt\", \"locator\": \"Figures 1a-b and 4; Results: inhibitor mechanism\", \"start_char\": 17453, \"end_char\": 22253}]\n[i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w","model_system":"Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"76da623d-a34a-5a5c-a942-d7571a85c486","stable_key":"import-aaa7baba-8689-56ab-ba1e-b71542bcb8e9","title":"Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"a4885eb6f58bad4a4514c958b63834619e57b10aa7f694aa97d0f65c7d36548f","revision_id":"ea8001a1-b576-5eda-a193-883c7ad59b73","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}