{"id":"58811b77-86a1-5177-94fe-eac68363aeb6","stable_key":"8182578e-8d21-598e-a3cb-e62d480d2251:myricetin-ape1-reassessment","predicate":"weak_under_aggregation_controls","statement":"In 2023, myricetin showed only weak APE1 inhibition at 0.33 mM with detergent/BSA, preventing an IC50 estimate; inhibition was much stronger without those additives.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"db56f626-d49e-56b6-bb76-854bc213fd30","mechanism_event_label":"Controlling compound aggregation changed the conclusion.","subject":{"id":"fafe05e7-4874-56e6-a42a-2ebf1ab2dd57","slug":"myricetin","display_name":"Myricetin","entity_type_key":"small_molecule"},"object":{"id":"4eef1de4-c3ff-555b-baaa-a48cf20def4f","slug":"apex1","display_name":"Human AP endonuclease 1 / APE1 / APEX1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"db56f626-d49e-56b6-bb76-854bc213fd30","stable_key":"8182578e-8d21-598e-a3cb-e62d480d2251:myricetin-ape1-reassessment-event","event_type":"observed_relationship","label":"Controlling compound aggregation changed the conclusion.","description":"In 2023, myricetin showed only weak APE1 inhibition at 0.33 mM with detergent/BSA, preventing an IC50 estimate; inhibition was much stronger without those additives.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"fafe05e7-4874-56e6-a42a-2ebf1ab2dd57","slug":"myricetin","display_name":"Myricetin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4eef1de4-c3ff-555b-baaa-a48cf20def4f","slug":"apex1","display_name":"Human AP endonuclease 1 / APE1 / APEX1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human APE1 delta-N38; UHPLC product assay and dynamic light scattering.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Authors propose nonspecific aggregation as an explanation for earlier potency. This is not a demonstrated explanation for every target in this chapter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"myricetin","display_name":"Myricetin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Controlling compound aggregation changed the conclusion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Characterizing inhibitors of human AP endonuclease 1. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36652434/ · DOI 10.1371/journal.pone.0280526","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5118d08f-9ac4-594f-aa38-813636b520b2","evidence_kind":"source_excerpt","locator":"Lines 660-666","start_line":660,"end_line":666,"excerpt":"## myricetin-ape1-reassessment\nControlling compound aggregation changed the conclusion.\nIn 2023, myricetin showed only weak APE1 inhibition at 0.33 mM with detergent/BSA, preventing an IC50 estimate; inhibition was much stronger without those additives.\nModel: Human APE1 delta-N38; UHPLC product assay and dynamic light scattering.\nLimitations: Authors propose nonspecific aggregation as an explanation for earlier potency. This is not a demonstrated explanation for every target in this chapter.\nEvidence access: Primary full text\nCharacterizing inhibitors of human AP endonuclease 1. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36652434/ · DOI 10.1371/journal.pone.0280526","model_system":"Human APE1 delta-N38; UHPLC product assay and dynamic light scattering.","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":"58045cd9-3b27-5469-bb4b-e1c6a9bdca34","stable_key":"import-8182578e-8d21-598e-a3cb-e62d480d2251","title":"Myricetin: metabolism, immune signaling, redox chemistry 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":"0abf512275cf3aae9e4ec8544f1cde97e0155d0cfb5be12a193cdd5a898386a7","revision_id":"422e342f-a55c-5e73-ba98-43df560f49b9","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"ad923580-9bdc-5f3f-a39b-a3c924f74a56","title":"Myricetin–APE1 inhibition: potent early result versus aggregation-controlled reassessment","kind":"contradiction","status":"open","why":"The 2009 study interpreted strong inhibition as APE1-targeted activity. The 2023 study directly challenged that potency and specificity, observing weak inhibition with aggregation controls and proposing nonspecific colloidal inhibition. Both are primary studies, not an editorial correction.","resolution":"Retain both. Treat myricetin as an unvalidated selective APE1 inhibitor. Repeat matched enzyme constructs, substrates, concentrations, detergent/BSA conditions and aggregation measurements before attributing cellular outcomes to APE1.","created_at":"2026-09-19 07:03:12","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/ad923580-9bdc-5f3f-a39b-a3c924f74a56","sides":[{"conflict_id":"ad923580-9bdc-5f3f-a39b-a3c924f74a56","ordinal":0,"label":"Original positive screen","revision_id":"422e342f-a55c-5e73-ba98-43df560f49b9","start_line":652,"end_line":658,"quote":"## myricetin-ape1-original\nAn early study identified a candidate DNA-repair inhibitor.\nThe 2009 screen reported potent myricetin inhibition of human APE1; radiotracer follow-up placed IC50 below 0.5 micromolar.\nModel: Purified enzyme and fluorescent/radiolabeled abasic-DNA incision assays.\nLimitations: Potency and target specificity were subsequently challenged by aggregation-controlled work; preserve this as a disputed result.\nEvidence access: Primary full text\nIdentification and characterization of inhibitors of human apurinic/apyrimidinic endonuclease APE1. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19484131/ · DOI 10.1371/journal.pone.0005740","source_key":"import-8182578e-8d21-598e-a3cb-e62d480d2251","source_title":"Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19)","claim_ids":["0b3d66e7-36a1-5fcc-be2b-945fac799fe0"]},{"conflict_id":"ad923580-9bdc-5f3f-a39b-a3c924f74a56","ordinal":1,"label":"Aggregation-controlled reassessment","revision_id":"422e342f-a55c-5e73-ba98-43df560f49b9","start_line":660,"end_line":666,"quote":"## myricetin-ape1-reassessment\nControlling compound aggregation changed the conclusion.\nIn 2023, myricetin showed only weak APE1 inhibition at 0.33 mM with detergent/BSA, preventing an IC50 estimate; inhibition was much stronger without those additives.\nModel: Human APE1 delta-N38; UHPLC product assay and dynamic light scattering.\nLimitations: Authors propose nonspecific aggregation as an explanation for earlier potency. This is not a demonstrated explanation for every target in this chapter.\nEvidence access: Primary full text\nCharacterizing inhibitors of human AP endonuclease 1. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36652434/ · DOI 10.1371/journal.pone.0280526","source_key":"import-8182578e-8d21-598e-a3cb-e62d480d2251","source_title":"Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19)","claim_ids":["58811b77-86a1-5177-94fe-eac68363aeb6"]}]}],"corrections":[],"research":null}