{"id":"f7df0996-29b7-5392-9a4b-bd928d58b613","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-renal-inhibition","predicate":"allosterically_inhibits","statement":"A designed inhibitor occupied an allosteric B0AT1 pocket about 17 angstroms from the substrate site, stabilized an outward-occluded state and blocked transport with submicromolar IC50.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"3f535a97-39d3-56ec-a267-d864720e8eeb","mechanism_event_label":"Transport can be blocked at a site away from where the amino acid binds.","subject":{"id":"55ca8a24-54c3-53ed-8650-7ea924fa4562","slug":"boat1-inhibitor-2026","display_name":"Experimental B0AT1 inhibitor from the 2026 structure-guided study","entity_type_key":"drug"},"object":{"id":"10307ad9-80a3-56be-a7f5-740c9362297f","slug":"slc6a19","display_name":"Human neutral amino acid transporter B0AT1 / SLC6A19","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"3f535a97-39d3-56ec-a267-d864720e8eeb","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-renal-inhibition-event","event_type":"observed_relationship","label":"Transport can be blocked at a site away from where the amino acid binds.","description":"A designed inhibitor occupied an allosteric B0AT1 pocket about 17 angstroms from the substrate site, stabilized an outward-occluded state and blocked transport with submicromolar IC50.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"55ca8a24-54c3-53ed-8650-7ea924fa4562","slug":"boat1-inhibitor-2026","display_name":"Experimental B0AT1 inhibitor from the 2026 structure-guided study","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"10307ad9-80a3-56be-a7f5-740c9362297f","slug":"slc6a19","display_name":"Human neutral amino acid transporter B0AT1 / SLC6A19","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human transporter cryo-EM and human/mouse transport inhibition assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Compound identity is not resolved in the accessed abstract; this is experimental pharmacology, not a supplement recommendation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Transport can be blocked at a site away from where the amino acid binds.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structure-guided development of a potent human B0AT1 inhibitor effective in a mouse model of phenylketonuria. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42350764/ · DOI 10.1038/s42003-026-10535-y","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fbe5ad26-50c8-5997-ac3c-a5f9599c1623","evidence_kind":"source_excerpt","locator":"Lines 174-180","start_line":174,"end_line":180,"excerpt":"## l-phenylalanine-renal-inhibition\nTransport can be blocked at a site away from where the amino acid binds.\nA designed inhibitor occupied an allosteric B0AT1 pocket about 17 angstroms from the substrate site, stabilized an outward-occluded state and blocked transport with submicromolar IC50.\nModel: Human transporter cryo-EM and human/mouse transport inhibition assays.\nLimitations: Compound identity is not resolved in the accessed abstract; this is experimental pharmacology, not a supplement recommendation.\nEvidence access: Primary abstract\nStructure-guided development of a potent human B0AT1 inhibitor effective in a mouse model of phenylketonuria. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42350764/ · DOI 10.1038/s42003-026-10535-y","model_system":"Human transporter cryo-EM and human/mouse transport inhibition assays.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"54de7c56-1e60-5d7b-8ef9-852c58ae92ba","stable_key":"import-56f1d914-e7da-595a-af69-c217b2b47407","title":"L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"4d53adcd4acc7a9aecf44ccb2623ec540c9d221a0f7c00002585870b39b8ffb8","revision_id":"fd182a81-4ab7-559a-9c77-fb4cf72982ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}