{"id":"75e06ca6-597d-5423-b1b9-6f2ea26ab6d3","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:tadalafil-inhibits-pde5","predicate":"inhibits","statement":"Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"6f33d7fc-faf4-5083-9f63-e1eda4806d0d","mechanism_event_label":"Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.","subject":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"object":{"id":"0be8b435-6b8a-592c-bd4c-c0efd9481a97","slug":"pde5-family","display_name":"Phosphodiesterase 5 family","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"6f33d7fc-faf4-5083-9f63-e1eda4806d0d","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:tadalafil-inhibits-pde5-event","event_type":"observed_relationship","label":"Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.","description":"Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0be8b435-6b8a-592c-bd4c-c0efd9481a97","slug":"pde5-family","display_name":"Phosphodiesterase 5 family","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6d2f509b-3a5b-5a38-b3e7-b148581edec9","slug":"cgmp","display_name":"Cyclic guanosine monophosphate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not applicable","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":"Isolated phosphodiesterase enzyme assays during medicinal-chemistry optimisation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Tadalafil, compound GF196960, the cis-(6R,12aR) enantiomer of the piperazinedione series","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"High diastereospecificity was observed in this series, so potency belongs to the named enantiomer and not to the racemate; selectivity was assessed against PDE1 to PDE4 and PDE6 in this report and not across all twelve families.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Isolated phosphodiesterase enzyme assays during medicinal-chemistry optimisation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Phosphodiesterase inhibition across isoenzymes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f7dc17e3-8f31-55e2-84af-56f71a65c990","evidence_kind":"source_excerpt","locator":"Lines 13-22","start_line":13,"end_line":22,"excerpt":"## tadalafil-inhibits-pde5\nTadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.\nModel/species: Isolated phosphodiesterase enzyme assays during medicinal-chemistry optimisation\nTissue/system: Phosphodiesterase inhibition across isoenzymes\nExposure: Tadalafil, compound GF196960, the cis-(6R,12aR) enantiomer of the piperazinedione series\nRoute: In vitro\nDuration: Not applicable\nLimits: High diastereospecificity was observed in this series, so potency belongs to the named enantiomer and not to the racemate; selectivity was assessed against PDE1 to PDE4 and PDE6 in this report and not across all twelve families.\nPrimary reference: The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"cca24ae7-e036-525c-a440-4cc2e38ccb4d","stable_key":"import-8ccb5461-efe2-5d95-9869-950d7cd50575","title":"Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22)","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. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text.","file_path":"","sha256":"3df8ec8f7114f983e8cae9fbc54912d3ac5b5f962454afea9dd8d4438c94cded","revision_id":"510acdea-65ae-57a6-b743-68e031ff1f05","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}