Deciphering biased inverse agonism of cangrelor and ticagrelor at P2Y₁₂ receptor.

ABSTRACT: P2Y₁₂ receptor (P2Y₁₂-R) is one of the major targets for drug inhibiting platelet aggregation in the treatment/prevention of arterial thrombosis. However, the clinical use of P2Y₁₂-R antagonists faces some limitations, such as a delayed onset of action (clopidogrel) or adverse effect profile (ticagrelor, cangrelor), justifying the development of a new generation of P2Y₁₂-R antagonists with a better clinical benefit-risk balance. Although the recent concept of biased agonism offers the possibility to alleviate undesirable adverse effects while preserving therapeutic outcomes, it has never been explored at P2Y₁₂-R. For the first time, using highly sensitive BRET2-based probes, we accurately delineated biased ligand efficacy at P2Y₁₂

SUBMITTER: Garcia C 

PROVIDER: S-EPMC11105710 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature