{"id":"dca49865-d40d-58d2-98e6-3a08e2a3107d","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:ces2-null","predicate":"no_detected_change_in_recorded_experiment","statement":"CES2 did not show comparable oseltamivir activation in the tested assays.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"e8071715-6798-55dc-819f-859078c43492","mechanism_event_label":"CES2 did not show comparable oseltamivir activation in the tested assays.","subject":{"id":"6ba9fe58-a85f-55bf-8959-d024eea12b78","slug":"human-ces2","display_name":"Human carboxylesterase 2 / CES2","entity_type_key":"protein"},"object":{"id":"14951488-ce25-5080-8278-5b39b5c8e2b2","slug":"oseltamivir-carboxylate","display_name":"Oseltamivir carboxylate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"e8071715-6798-55dc-819f-859078c43492","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:ces2-null-event","event_type":"experimental_observation","label":"CES2 did not show comparable oseltamivir activation in the tested assays.","description":"**The prodrug has its own activation mechanism.** The oseltamivir prodrug is hydrolyzed to oseltamivir carboxylate by human CES1 in the studied human-liver/recombinant systems. CES2, intestinal microsomes and plasma did not show comparable activation in those assays. An in-vitro clopidogrel inhibition observation does not by itself establish loss of antiviral treatment efficacy; subsequent correspondence concerns that translation. These records belong to oseltamivir and CES1, not to a fictitious human shikimate-to-drug reaction. [Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel.](https://pubmed.ncbi.nlm.nih.gov/16966469/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6ba9fe58-a85f-55bf-8959-d024eea12b78","slug":"human-ces2","display_name":"Human carboxylesterase 2 / CES2","entity_type_key":"protein"},"role":"tested factor","stoichiometry":null,"state_label":"as reported","sequence_order":0,"notes":""},{"entity":{"id":"14951488-ce25-5080-8278-5b39b5c8e2b2","slug":"oseltamivir-carboxylate","display_name":"Oseltamivir carboxylate","entity_type_key":"small_molecule"},"role":"measured outcome","stoichiometry":null,"state_label":"no_detected_change","sequence_order":1,"notes":""},{"entity":{"id":"ca29fbe2-9ef6-56c9-9a85-f884381de177","slug":"oseltamivir","display_name":"Oseltamivir","entity_type_key":"small_molecule"},"role":"tested prodrug","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human esterase comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Assay-specific lack of conversion; not a general lack of CES2 activity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"CES2 did not show comparable oseltamivir activation in the tested assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. | 2006 | DOI 10.1124/jpet.106.111807 | PMID 16966469 | https://pubmed.ncbi.nlm.nih.gov/16966469/ | https://doi.org/10.1124/jpet.106.111807","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 45-45; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"df75a660-8ebb-5496-a545-f736c0d84a8a","evidence_kind":"source_excerpt","locator":"Lines 45-45","start_line":45,"end_line":45,"excerpt":"**The prodrug has its own activation mechanism.** The oseltamivir prodrug is hydrolyzed to oseltamivir carboxylate by human CES1 in the studied human-liver/recombinant systems. CES2, intestinal microsomes and plasma did not show comparable activation in those assays. An in-vitro clopidogrel inhibition observation does not by itself establish loss of antiviral treatment efficacy; subsequent correspondence concerns that translation. These records belong to oseltamivir and CES1, not to a fictitious human shikimate-to-drug reaction. [Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel.](https://pubmed.ncbi.nlm.nih.gov/16966469/)","model_system":"Recombinant human esterase comparison.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e6ae59de-0369-5c2f-8262-57d91302671c","stable_key":"import-31b1baa4-4113-5541-b9e7-fe44a5253a07","title":"Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026)","document_type":"imported_text","citation_label":"Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication.","file_path":"","sha256":"95b1f9e9577661312d67f36e156d2e49326b207f296c1c0e801a5b007fd8e283","revision_id":"cd3237f1-131a-557d-84b5-7543259807b0","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}