{"id":"23b79bc8-0fff-541d-adda-f552e9d125bb","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-ido-drug-bypass","predicate":"not_blocked_by_ido_inhibitors","statement":"IDO1 inhibitors did not block IL4I1 in the study, leaving an alternative route to AHR activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"09abce3d-60be-5727-ba0f-93b140116ef2","mechanism_event_label":"Blocking one enzyme does not necessarily close a parallel route.","subject":{"id":"acbbf0c2-4c0f-5fc6-86ac-e817647db149","slug":"il4i1","display_name":"Human interleukin-4-induced protein 1 / IL4I1","entity_type_key":"protein"},"object":{"id":"757ea2d0-1c8e-5453-a721-4a3a3443a383","slug":"ahr","display_name":"Human aryl hydrocarbon receptor / AHR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"09abce3d-60be-5727-ba0f-93b140116ef2","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-ido-drug-bypass-event","event_type":"observed_relationship","label":"Blocking one enzyme does not necessarily close a parallel route.","description":"IDO1 inhibitors did not block IL4I1 in the study, leaving an alternative route to AHR activation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"acbbf0c2-4c0f-5fc6-86ac-e817647db149","slug":"il4i1","display_name":"Human interleukin-4-induced protein 1 / IL4I1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"757ea2d0-1c8e-5453-a721-4a3a3443a383","slug":"ahr","display_name":"Human aryl hydrocarbon receptor / AHR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9edba4aa-c2f5-5a4e-9750-15e9a38b1822","slug":"ido1","display_name":"Human indoleamine 2,3-dioxygenase 1 / IDO1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cancer-mechanism experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An explanation proposed for clinical trial failure, not proof that IL4I1 caused failure in every patient.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Blocking one enzyme does not necessarily close a parallel route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32818467/ · DOI 10.1016/j.cell.2020.07.038","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"34febb75-509e-5644-a84e-98457d3d3f65","evidence_kind":"source_excerpt","locator":"Lines 458-464","start_line":458,"end_line":464,"excerpt":"## tryptophan-ido-drug-bypass\nBlocking one enzyme does not necessarily close a parallel route.\nIDO1 inhibitors did not block IL4I1 in the study, leaving an alternative route to AHR activation.\nModel: Cancer-mechanism experiments.\nLimitations: An explanation proposed for clinical trial failure, not proof that IL4I1 caused failure in every patient.\nEvidence access: Primary abstract\nIL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32818467/ · DOI 10.1016/j.cell.2020.07.038","model_system":"Cancer-mechanism experiments.","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":"73f9d3e7-fdc9-5418-8f3c-f4ef145f6efa","stable_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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