{"id":"55c8c0b9-a81d-5718-93da-0e37b67d6714","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:opc-u0126","predicate":"reported_relationship","statement":"The SA-associated MBP increase persisted in the presence of U0126.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"ee53bd87-12f6-5862-9530-b97f0a93da55","mechanism_event_label":"The SA-associated MBP increase persisted in the presence of U0126.","subject":{"id":"9827a659-c7a9-5709-b251-e8c6082bd8f6","slug":"u0126","display_name":"U0126 MEK-pathway inhibitor","entity_type_key":"small_molecule"},"object":{"id":"f6d3d9d8-1cba-59d7-973a-b7decec87431","slug":"rat-mbp","display_name":"Rat myelin basic protein / Mbp","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ee53bd87-12f6-5862-9530-b97f0a93da55","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:opc-u0126-event","event_type":"experimental_observation","label":"The SA-associated MBP increase persisted in the presence of U0126.","description":"**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9827a659-c7a9-5709-b251-e8c6082bd8f6","slug":"u0126","display_name":"U0126 MEK-pathway inhibitor","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"u0126 plus SA","sequence_order":0,"notes":""},{"entity":{"id":"f6d3d9d8-1cba-59d7-973a-b7decec87431","slug":"rat-mbp","display_name":"Rat myelin basic protein / Mbp","entity_type_key":"protein"},"role":"measured outcome","stoichiometry":null,"state_label":"not_reported","sequence_order":1,"notes":""},{"entity":{"id":"67ad4a8f-1bf6-59e5-90a6-97b7709024d3","slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"},"role":"joint exposure","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"present","comparator":"SA without the inhibitor","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"}},{"dimension":"experimental_condition","value_text":"present","comparator":"SA without the inhibitor","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"u0126","display_name":"U0126 MEK-pathway inhibitor","entity_type_key":"small_molecule"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"u0126 plus SA\", \"comparator\": \"SA without the inhibitor\", \"endpoint\": \"The SA-associated MBP increase persisted in the presence of U0126.\", \"effect_direction\": \"not_reported\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"u0126\", \"state\": \"present\"}, {\"entity_slug\": \"shikimic-acid\", \"state\": \"present\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Primary rat OPC joint exposure, 100 µg/mL SA.","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":"Persistence with U0126 is not a blanket null for MEK activity. Inhibitors do not identify the direct SA target.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The SA-associated MBP increase persisted in the presence of U0126.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 71-71; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"362334d3-040e-5bd6-b2f0-60ddd2fbcd45","evidence_kind":"source_excerpt","locator":"Lines 71-71","start_line":71,"end_line":71,"excerpt":"**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)","model_system":"Primary rat OPC joint exposure, 100 µg/mL SA.","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. 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