{"id":"0c56264b-8b3c-5739-a1b5-3fedfddb6574","stable_key":"c8c7aa13-14c6-5f5c-9afc-9217d0f2f736:hfcs-pf-hepatocytes","predicate":"inhibits","statement":"PF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"3225a47b-234a-569b-8d8e-2b845c3164f6","mechanism_event_label":"PF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes.","subject":{"id":"2bddbb8e-14f7-5d4d-a89e-65ed95a2b3da","slug":"pf-06835919","display_name":"PF-06835919","entity_type_key":"drug"},"object":{"id":"1f163f85-1330-5148-a913-a32f189855ad","slug":"human-hepatocyte-fructose1p-formation","display_name":"Fructose-1-phosphate formation in primary human hepatocytes","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3225a47b-234a-569b-8d8e-2b845c3164f6","stable_key":"c8c7aa13-14c6-5f5c-9afc-9217d0f2f736:hfcs-pf-hepatocytes-event","event_type":"observed_relationship","label":"PF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes.","description":"PF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2bddbb8e-14f7-5d4d-a89e-65ed95a2b3da","slug":"pf-06835919","display_name":"PF-06835919","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1f163f85-1330-5148-a913-a32f189855ad","slug":"human-hepatocyte-fructose1p-formation","display_name":"Fructose-1-phosphate formation in primary human hepatocytes","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3c379840-5688-5b5d-84c0-5950b4fd8f17","slug":"fructose","display_name":"Fructose","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a273c7f5-e73a-5464-8947-f2d52f201d88","slug":"fructose-1-phosphate","display_name":"D-Fructose 1-phosphate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"599b478d-692a-5baa-a176-ea5f55769e74","slug":"khk","display_name":"Human ketohexokinase / KHK","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"dose","value_text":"PF-06835919 concentration series; 10 mM labeled fructose","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"30 min pretreatment; 20 min fructose reaction","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary full-text methods/results and metadata inspected.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"literature_reviewed; source-specific curation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Primary human hepatocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure_scope","value_text":"Isolated fructose / investigational drug","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Functional KHK inhibition in cells; PF-06835919 is investigational. Study sponsored/conducted by industry; pharmacological target engagement is not dietary efficacy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished.","comparator":null,"unit":null,"notes":"","entity":{"slug":"high-fructose-corn-syrup","display_name":"High-Fructose Corn Syrup / HFCS","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Primary human hepatocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"PF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction. (2021). https://pubmed.ncbi.nlm.nih.gov/33667726/ DOI: 10.1016/j.molmet.2021.101196","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro inhibitor pretreatment and fructose addition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Labeled fructose-1-phosphate production","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"831dc763-d1ca-5dbd-9c2f-a1468a0b924a","evidence_kind":"source_excerpt","locator":"Lines 569-579","start_line":569,"end_line":579,"excerpt":"## hfcs-pf-hepatocytes\nPF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes.\nModel/species: Primary human hepatocytes\nTissue: Labeled fructose-1-phosphate production\nExposure: PF-06835919 concentration series; 10 mM labeled fructose\nRoute: In vitro inhibitor pretreatment and fructose addition\nDuration: 30 min pretreatment; 20 min fructose reaction\nExposure scope: Isolated fructose / investigational drug\nLimits: Functional KHK inhibition in cells; PF-06835919 is investigational. Study sponsored/conducted by industry; pharmacological target engagement is not dietary efficacy.\nReference: Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction. (2021). https://pubmed.ncbi.nlm.nih.gov/33667726/ DOI: 10.1016/j.molmet.2021.101196\nAccess: Primary full-text methods/results and metadata inspected.","model_system":"Primary human hepatocytes","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact original curation span, not a publisher quotation; provenance retained.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e863ddf6-7c1e-5a70-8335-7f3ac3eeee92","stable_key":"import-c8c7aa13-14c6-5f5c-9afc-9217d0f2f736","title":"High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. 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