{"id":"e6318aca-36e4-5bd5-af79-08f5f4d09cac","stable_key":"f2ec2007-88ff-5a96-a73b-8b5085e9cea9:mbz-the-5-substituent-governs","predicate":"is_modulated_by","statement":"Across thirty-two methyl benzimidazol-2-yl carbamates, the size or some colinear physico-chemical characteristic of the substituent in the 5 or 6 position had a profound effect on potency against mammalian tubulin polymerisation, and branching with or without a commensurate increase in polarity adjacent to the benzimidazole ring resulted in a loss of activity.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7145054a-1d14-5307-b92b-0d9f30f91d1c","mechanism_event_label":"One position on the ring decides how well the whole family works.","subject":{"id":"f8582a13-fc2e-5127-a61f-5b0594e54069","slug":"mebendazole","display_name":"Mebendazole","entity_type_key":"drug"},"object":{"id":"011e92dc-f29a-5ed1-bc3e-942ffc6664bb","slug":"microtubule-polymerisation","display_name":"Polymerisation of tubulin into microtubules","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7145054a-1d14-5307-b92b-0d9f30f91d1c","stable_key":"f2ec2007-88ff-5a96-a73b-8b5085e9cea9:mbz-the-5-substituent-governs-event","event_type":"observed_intervention","label":"One position on the ring decides how well the whole family works.","description":"Across thirty-two methyl benzimidazol-2-yl carbamates, the size or some colinear physico-chemical characteristic of the substituent in the 5 or 6 position had a profound effect on potency against mammalian tubulin polymerisation, and branching with or without a commensurate increase in polarity adjacent to the benzimidazole ring resulted in a loss of activity.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d67b7610-905f-5e26-bdde-06d7fc12d8e8","slug":"carbendazim","display_name":"Carbendazim","entity_type_key":"chemical_species"},"role":"parent_scaffold","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f8582a13-fc2e-5127-a61f-5b0594e54069","slug":"mebendazole","display_name":"Mebendazole","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"011e92dc-f29a-5ed1-bc3e-942ffc6664bb","slug":"microtubule-polymerisation","display_name":"Polymerisation of tubulin into microtubules","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/mebendazole-research/3985991.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9b881308a6051bd89e2f8323670dd08a8d5e50cf06c7705724ece611440643e5\", \"start_char\": 0, \"end_char\": 680, \"text_sha256\": \"9b881308a6051bd89e2f8323670dd08a8d5e50cf06c7705724ece611440643e5\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Structure-activity study of thirty-two methyl benzimidazol-2-yl carbamates against mammalian tubulin polymerisation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Systematic variation of the 5(6)-position substituent","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Quantitative structure-activity modelling on the off-target protein. It says which part of the molecule matters, not which target matters.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms.","comparator":null,"unit":null,"notes":"","entity":{"slug":"mebendazole","display_name":"Mebendazole","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Mammal","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"One position on the ring decides how well the whole family works.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mbz-p3985991] Structure-activity relationships of benzimidazole carbamates as inhibitors of mammalian tubulin, in vitro. (1985). https://pubmed.ncbi.nlm.nih.gov/3985991/ DOI: 10.1016/0006-2952(85)90611-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Tubulin","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ef0ee7fd-6d97-585d-a3db-304ba762ca29","evidence_kind":"source_excerpt","locator":"Lines 225-236","start_line":225,"end_line":236,"excerpt":"### mbz-the-5-substituent-governs\nAcross thirty-two methyl benzimidazol-2-yl carbamates, the size or some colinear physico-chemical characteristic of the substituent in the 5 or 6 position had a profound effect on potency against mammalian tubulin polymerisation, and branching with or without a commensurate increase in polarity adjacent to the benzimidazole ring resulted in a loss of activity.\nCondition category: normal\nnutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms.\nplain_language: One position on the ring decides how well the whole family works.\norganism: Mammal\ntissue_or_cell_type: Tubulin\nexperimental_model: Structure-activity study of thirty-two methyl benzimidazol-2-yl carbamates against mammalian tubulin polymerisation\nlimitations: Quantitative structure-activity modelling on the off-target protein. It says which part of the molecule matters, not which target matters.\nexposure: Systematic variation of the 5(6)-position substituent\nevidence_span: {\"source_cache\": \"artifacts/mebendazole-research/3985991.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9b881308a6051bd89e2f8323670dd08a8d5e50cf06c7705724ece611440643e5\", \"start_char\": 0, \"end_char\": 680, \"text_sha256\": \"9b881308a6051bd89e2f8323670dd08a8d5e50cf06c7705724ece611440643e5\"}\n[mbz-p3985991] Structure-activity relationships of benzimidazole carbamates as inhibitors of mammalian tubulin, in vitro. 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