Year: 2020
Type: article
Abstract: The P2Y1 receptor (P2Y1R) is a G protein-coupled receptor naturally activated by extracellular ADP. Its stimulation is an essential requirement of ADP-induced platelet aggregation, thus making antagonists highly sought compounds for the development of antithrombotic agents. Here, through a virtual screening campaign based on a pharmacophoric representation of the common characteristics of known P2Y1R ligands and the putative shape and size of the receptor binding pocket, we have identified novel antagonist hits of µM affinity derived from a N,N’-bis-arylurea chemotype. Unlike the vast majority of known P2Y1R antagonists, these drug-like compounds do not have a nucleotidic scaffold or highly negatively charged phosphate groups. Hence, our compounds may provide a direction for the development of receptor probes with altered physicochemical properties.
DOI: 10.17615/tjj0-qf07
Authors: Costanzi, Stefano, Santhosh Kumar, T., Balasubramanian, Ramachandran, Jacobson, Kenneth A., Kendall Harden, T.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Physiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4298185059