{"id":"80e7312e-ef34-547a-a412-716bba7d8198","stable_key":"9a47f338-d127-5e4d-abf6-e99056833a69:d-aspartate-olanzapine-human-ddo","predicate":"inhibits_tested","statement":"Olanzapine inhibited recombinant human DDO at an IC50 near 23 micromolar under both 4 and 100 micromolar FAD conditions; clozapine did not inhibit the tested enzyme.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a3012fea-c995-5bcc-a108-8581d8da5d87","mechanism_event_label":"Two drugs differed at a D-aspartate-clearing enzyme.","subject":{"id":"e83902e5-cd44-5de2-b790-abf19033d265","slug":"olanzapine","display_name":"Olanzapine","entity_type_key":"small_molecule"},"object":{"id":"17871951-099f-5a48-832e-ff9cb1c65755","slug":"ddo","display_name":"Human D-aspartate oxidase / DDO","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"a3012fea-c995-5bcc-a108-8581d8da5d87","stable_key":"9a47f338-d127-5e4d-abf6-e99056833a69:d-aspartate-olanzapine-human-ddo-event","event_type":"observed_relationship","label":"Two drugs differed at a D-aspartate-clearing enzyme.","description":"Olanzapine inhibited recombinant human DDO at an IC50 near 23 micromolar under both 4 and 100 micromolar FAD conditions; clozapine did not inhibit the tested enzyme.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e83902e5-cd44-5de2-b790-abf19033d265","slug":"olanzapine","display_name":"Olanzapine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"17871951-099f-5a48-832e-ff9cb1c65755","slug":"ddo","display_name":"Human D-aspartate oxidase / DDO","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b3404670-6db1-517f-b9a0-27ecfaac558b","slug":"d-aspartate","display_name":"D-Aspartate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"2131891d-599e-5f0d-99f2-641cbbae52a7","slug":"clozapine","display_name":"Clozapine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human DDO drug concentration-response assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biochemical potency is not proof of clinically relevant brain inhibition or a reason to change treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"d-aspartate","display_name":"D-Aspartate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Two drugs differed at a D-aspartate-clearing enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0fe8cceb-6642-5bf0-8966-9e4dde86a97c","evidence_kind":"source_excerpt","locator":"Lines 264-270","start_line":264,"end_line":270,"excerpt":"## d-aspartate-olanzapine-human-ddo\nTwo drugs differed at a D-aspartate-clearing enzyme.\nOlanzapine inhibited recombinant human DDO at an IC50 near 23 micromolar under both 4 and 100 micromolar FAD conditions; clozapine did not inhibit the tested enzyme.\nModel: Purified human DDO drug concentration-response assay.\nLimitations: Biochemical potency is not proof of clinically relevant brain inhibition or a reason to change treatment.\nEvidence access: Primary full text\nOlanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288","model_system":"Purified human DDO drug concentration-response assay.","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":"3751103e-e256-5615-b24f-39cc76ccfb47","stable_key":"import-9a47f338-d127-5e4d-abf6-e99056833a69","title":"D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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