{"id":"e0fe6401-c976-580c-aca1-b793b9eb12fb","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:cyclosporine-forms-the-inhibitory-complex","predicate":"forms","statement":"The effects of cyclosporin A are reported to follow from the formation of an inhibitory complex between the drug and its prolyl isomerase, and not from inhibition of the isomerase activity that drug binding also causes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"89322fba-005b-5fdf-9503-bb7660f1ea04","mechanism_event_label":"The effects of cyclosporin A are reported to follow from the formation of an inhibitory complex between the drug and its prolyl isomerase, and not from inhibition of the isomerase activity that drug b","subject":{"id":"b199063a-fae6-5c5c-9cb4-22c10453bbac","slug":"cyclosporine","display_name":"Cyclosporine","entity_type_key":"drug"},"object":{"id":"90dbcd2a-88d9-5a7f-85b2-5372761d4b4e","slug":"cyclophilin-a-cyclosporine","display_name":"Cyclophilin A-cyclosporine complex","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"89322fba-005b-5fdf-9503-bb7660f1ea04","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:cyclosporine-forms-the-inhibitory-complex-event","event_type":"biochemical_relationship","label":"The effects of cyclosporin A are reported to follow from the formation of an inhibitory complex between the drug and its prolyl isomerase, and not from inhibition of the isomerase activity that drug b","description":"Formation of the drug-immunophilin complex","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b199063a-fae6-5c5c-9cb4-22c10453bbac","slug":"cyclosporine","display_name":"Cyclosporine","entity_type_key":"drug"},"role":"acting component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"90dbcd2a-88d9-5a7f-85b2-5372761d4b4e","slug":"cyclophilin-a-cyclosporine","display_name":"Cyclophilin A-cyclosporine complex","entity_type_key":"protein_complex"},"role":"component the finding is about","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not stated here","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mammalian immunophilin biochemistry, with cyclosporin-resistant yeast mutants cited as support","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cyclosporin A with cyclophilin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is the step that makes the drug an inhibitor of anything, and it is why no arrow in this collection runs from cyclosporine to calcineurin directly. The evidence cited for it in this report is the behaviour of other isomerase inhibitors and of cyclosporin-resistant yeast mutants, which is an argument from the pattern of results rather than a measurement of complex formation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mammalian immunophilin biochemistry, with cyclosporin-resistant yeast mutants cited as support","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The effects of cyclosporin A are reported to follow from the formation of an inhibitory complex between the drug and its prolyl isomerase, and not from inhibition of the isomerase activity that drug binding also causes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. (1991). https://pubmed.ncbi.nlm.nih.gov/1715516/ DOI: 10.1038/352803a0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Formation of the drug-immunophilin complex","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c72ac91f-b54e-55da-a0c6-6a721321202d","evidence_kind":"source_excerpt","locator":"Lines 25-25","start_line":25,"end_line":25,"excerpt":"The effects of cyclosporin A are reported to follow from the formation of an inhibitory complex between the drug and its prolyl isomerase, and not from inhibition of the isomerase activity that drug binding also causes.","model_system":"Mammalian immunophilin biochemistry, with cyclosporin-resistant yeast mutants cited as support","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"6b2b7746-fc66-5491-b896-e6261df254c9","stable_key":"import-1bbf9d44-8d2b-5b35-8f82-f6876558b0b3","title":"Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text.","file_path":"","sha256":"499d00555a629cba2271c3888d7e93627949891d565c4c78c843610de2913080","revision_id":"263ee68a-4184-51d0-a977-197d7ddb7a4d","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}