{"id":"ad299d4e-8560-5aa6-aa36-4842e63aa2a3","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-ipa-human-pxr","predicate":"weakly_activates","statement":"Indolepropionate alone weakly activated human PXR, with an EC50 near 120 micromolar; adding 1 mM indole enhanced activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c42d7fa7-3dba-5ebd-b494-de874813628e","mechanism_event_label":"A partner microbial metabolite changed the human receptor response.","subject":{"id":"813fc8bf-f15a-5201-91e3-d1579084376d","slug":"indole-3-propionic-acid","display_name":"Indole-3-propionic acid / indolepropionate","entity_type_key":"small_molecule"},"object":{"id":"f9deea3c-fcb8-51c8-9194-438c2ad6298b","slug":"nr1i2","display_name":"Human pregnane X receptor / SXR / PXR / NR1I2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"c42d7fa7-3dba-5ebd-b494-de874813628e","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-ipa-human-pxr-event","event_type":"observed_relationship","label":"A partner microbial metabolite changed the human receptor response.","description":"Indolepropionate alone weakly activated human PXR, with an EC50 near 120 micromolar; adding 1 mM indole enhanced activation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"813fc8bf-f15a-5201-91e3-d1579084376d","slug":"indole-3-propionic-acid","display_name":"Indole-3-propionic acid / indolepropionate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f9deea3c-fcb8-51c8-9194-438c2ad6298b","slug":"nr1i2","display_name":"Human pregnane X receptor / SXR / PXR / NR1I2","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":"456cd56f-01cb-5202-bb9d-86824e845498","slug":"indole","display_name":"Indole","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text, Figure 1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human PXR reporter in 293T cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Millimolar indole is an assay condition, not a verified systemic human exposure.","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":"A partner microbial metabolite changed the human receptor response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25065623/ · DOI 10.1016/j.immuni.2014.06.014","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"27dfd7fd-be4f-5c9a-8f09-0387bf7596ec","evidence_kind":"source_excerpt","locator":"Lines 530-536","start_line":530,"end_line":536,"excerpt":"## tryptophan-ipa-human-pxr\nA partner microbial metabolite changed the human receptor response.\nIndolepropionate alone weakly activated human PXR, with an EC50 near 120 micromolar; adding 1 mM indole enhanced activation.\nModel: Human PXR reporter in 293T cells.\nLimitations: Millimolar indole is an assay condition, not a verified systemic human exposure.\nEvidence access: Primary full text, Figure 1\nSymbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25065623/ · DOI 10.1016/j.immuni.2014.06.014","model_system":"Human PXR reporter in 293T cells.","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. Not publisher full text.","file_path":"","sha256":"7dfd20063b91900cb5c6ad675e3e675b7e25ef0fb8304eabac6f263cc5518284","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}