{"id":"3838c89f-b4be-5927-8150-5254d175e295","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-metformin-fxr-target-genes","predicate":"inhibits","statement":"Metformin inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"f6f325d6-36b1-5094-aec6-605063b6d2d3","mechanism_event_label":"The drug reaches that receptor’s gene programme in both organs.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"d6318511-41c0-5530-92b3-9c2fe178ea38","slug":"fxr-transcriptional-activity","display_name":"FXR transcriptional activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f6f325d6-36b1-5094-aec6-605063b6d2d3","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-metformin-fxr-target-genes-event","event_type":"biochemical_relationship","label":"The drug reaches that receptor’s gene programme in both organs.","description":"Metformin inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d6318511-41c0-5530-92b3-9c2fe178ea38","slug":"fxr-transcriptional-activity","display_name":"FXR transcriptional activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/24531544.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9e34abf954452e017d254058f7e611697560bba87a53cf726c88f0b77d6673ad\", \"start_char\": 0, \"end_char\": 1358, \"text_sha256\": \"9e34abf954452e017d254058f7e611697560bba87a53cf726c88f0b77d6673ad\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mass-spectrometry interaction screen in human hepatoma cells with mouse liver, intestine and a cholestasis model","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin and other AMPK activators with FXR agonists","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An adverse-direction finding: in a cholestasis model metformin worsened liver injury. Recorded because a mechanism record should not be filtered for favourable outcomes.","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 cells and mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The drug reaches that receptor’s gene programme in both organs.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p24531544] Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk. 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Recorded because a mechanism record should not be filtered for favourable outcomes.\nexposure: Metformin and other AMPK activators with FXR agonists\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/24531544.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9e34abf954452e017d254058f7e611697560bba87a53cf726c88f0b77d6673ad\", \"start_char\": 0, \"end_char\": 1358, \"text_sha256\": \"9e34abf954452e017d254058f7e611697560bba87a53cf726c88f0b77d6673ad\"}\n[metformin-p24531544] Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk. (2014). https://pubmed.ncbi.nlm.nih.gov/24531544/ DOI: 10.1172/jci68815","model_system":"Mass-spectrometry interaction screen in human hepatoma cells with mouse liver, intestine and a cholestasis model","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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