{"id":"90fec9bd-0d79-5136-a6eb-20c235491965","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-mtx-tmp-transport-competition","predicate":"inhibits","statement":"Methotrexate inhibited the RFC-mediated component of thiamine-monophosphate influx in mouse L1210 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"1bc9b47b-cb16-52ab-80ef-59b8da4c70f8","mechanism_event_label":"An antifolate competed with phosphorylated B1 entry.","subject":{"id":"1f13ebf9-42c9-516e-b462-0e1b3952c2a2","slug":"methotrexate","display_name":"Methotrexate","entity_type_key":"small_molecule"},"object":{"id":"2d52919c-025a-5772-92b0-6229c0b74ba3","slug":"thiamine-monophosphate","display_name":"Thiamine monophosphate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"1bc9b47b-cb16-52ab-80ef-59b8da4c70f8","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-mtx-tmp-transport-competition-event","event_type":"biochemical_relationship","label":"An antifolate competed with phosphorylated B1 entry.","description":"Methotrexate inhibited the RFC-mediated component of thiamine-monophosphate influx in mouse L1210 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1f13ebf9-42c9-516e-b462-0e1b3952c2a2","slug":"methotrexate","display_name":"Methotrexate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2d52919c-025a-5772-92b0-6229c0b74ba3","slug":"thiamine-monophosphate","display_name":"Thiamine monophosphate","entity_type_key":"small_molecule"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"91f4365d-4a71-564a-a40d-088e23f03914","slug":"mouse-slc19a1","display_name":"Mouse reduced folate carrier / Slc19a1","entity_type_key":"protein"},"role":"shared transporter","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"B1-antifolate: competition at RFC under the tested drug exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse L1210/R16 leukemia transport experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"50 nM TMP with 100 micromolar methotrexate","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological cell experiment, not a clinical thiamine-deficiency outcome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An antifolate competed with phosphorylated B1 entry.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zhao2002] Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells (2002). https://pubmed.ncbi.nlm.nih.gov/11997266/ DOI: 10.1152/ajpcell.00547.2001","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"L1210 leukemia cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"28f536c2-beac-51cd-9ccd-9dd475dcd892","evidence_kind":"source_excerpt","locator":"Lines 193-204","start_line":193,"end_line":204,"excerpt":"### folate-mtx-tmp-transport-competition\nMethotrexate inhibited the RFC-mediated component of thiamine-monophosphate influx in mouse L1210 cells.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An antifolate competed with phosphorylated B1 entry.\norganism: Mus musculus\ntissue_or_cell_type: L1210 leukemia cells\nexperimental_model: Mouse L1210/R16 leukemia transport experiments\nlimitations: Pharmacological cell experiment, not a clinical thiamine-deficiency outcome.\nexposure: 50 nM TMP with 100 micromolar methotrexate\ncross_nutrient: B1-antifolate: competition at RFC under the tested drug exposure.\n[zhao2002] Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells (2002). https://pubmed.ncbi.nlm.nih.gov/11997266/ DOI: 10.1152/ajpcell.00547.2001","model_system":"Mouse L1210/R16 leukemia transport experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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