{"id":"7741e197-52b1-5300-b69e-3d3efd33314c","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-metformin-inhibits-thtr2","predicate":"inhibits","statement":"Metformin, along with phenformin, chloroquine, verapamil, famotidine and amprolium, inhibited hTHTR-2-mediated uptake of both thiamine and metformin.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"397607c8-ff2d-524c-892a-b500b11d2661","mechanism_event_label":"Because they share the carrier, the drug gets in the vitamin’s way.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"79bf8987-06cf-5d7c-8f8a-71fe7f9c2698","slug":"intestinal-thiamine-uptake","display_name":"Intestinal free-thiamine uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"397607c8-ff2d-524c-892a-b500b11d2661","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-metformin-inhibits-thtr2-event","event_type":"biochemical_relationship","label":"Because they share the carrier, the drug gets in the vitamin’s way.","description":"Metformin, along with phenformin, chloroquine, verapamil, famotidine and amprolium, inhibited hTHTR-2-mediated uptake of both thiamine and metformin.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4eba176e-17c8-5515-920a-df5d48a40486","slug":"slc19a3","display_name":"Human thiamine transporter 2 / SLC19A3","entity_type_key":"protein"},"role":"shared_transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"displaced_nutrient","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"79bf8987-06cf-5d7c-8f8a-71fe7f9c2698","slug":"intestinal-thiamine-uptake","display_name":"Intestinal free-thiamine uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/26528626.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\", \"start_char\": 0, \"end_char\": 1436, \"text_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transporter uptake assays in cells expressing human THTR-1 and THTR-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin against thiamine uptake by SLC19A2 and SLC19A3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"metformin","display_name":"Metformin","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human transporters, with mouse orthologue comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Because they share the carrier, the drug gets in the vitamin’s way.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Small-intestinal absorption","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"05155908-84fd-58be-b5b2-994eff28c539","evidence_kind":"source_excerpt","locator":"Lines 1295-1306","start_line":1295,"end_line":1306,"excerpt":"### metformin-metformin-inhibits-thtr2\nMetformin, along with phenformin, chloroquine, verapamil, famotidine and amprolium, inhibited hTHTR-2-mediated uptake of both thiamine and metformin.\nCondition category: nutrient_deficiency\nnutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.\nplain_language: Because they share the carrier, the drug gets in the vitamin’s way.\norganism: Human transporters, with mouse orthologue comparison\ntissue_or_cell_type: Small-intestinal absorption\nexperimental_model: Transporter uptake assays in cells expressing human THTR-1 and THTR-2\nlimitations: In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.\nexposure: Metformin against thiamine uptake by SLC19A2 and SLC19A3\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/26528626.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\", \"start_char\": 0, \"end_char\": 1436, \"text_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\"}\n[metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501","model_system":"Transporter uptake assays in cells expressing human THTR-1 and THTR-2","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d0474bd9-7cfd-5695-a152-12f3633a6813","stable_key":"import-8b3cf083-ea9c-54f5-b42b-bf1fef5b2978","title":"Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19)","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":"0b51d0759aeeb88ac5b3a6277245a196b2bb024d7c32ec89379ed428fb06bfb5","revision_id":"0405c75e-f06e-5af7-a642-1777802f6004","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}