Identification of determinants required for agonistic and inverse agonistic ligand properties at the ADP receptor P2Y12.

ABSTRACT: The ADP receptor P2Y(12) belongs to the superfamily of G protein-coupled receptors (GPCRs), and its activation triggers platelet aggregation. Therefore, potent antagonists, such as clopidogrel, are of high clinical relevance in prophylaxis and treatment of thromboembolic events. P2Y(12) displays an elevated basal activity in vitro, and as such, inverse agonists may be therapeutically beneficial compared with antagonists. Only a few inverse agonists of P2Y(12) have been described. To expand this limited chemical space and improve understanding of structural determinants of inverse agonist-receptor interaction, this study screened a purine compound library for lead structures using wild-type (WT) human P2Y(12) and 28 constitutively active mutants. Results showed that ATP and ATP derivatives

SUBMITTER: Schmidt P 

PROVIDER: S-EPMC3533468 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature