P2Y nucleotide receptors: promise of therapeutic applications

Abstract

Extracellular nucleotides, such as ATP and UTP, have distinct signaling roles through a class of G-protein-coupled receptors, termed P2Y. The receptor ligands are typically charged molecules of low bioavailability and stability in vivo. Recent progress in the development of selective agonists and antagonists for P2Y receptors and study of knockout mice have led to new drug concepts based on these receptors. The rapidly accelerating progress in this field has already resulted in drug candidates for cystic fibrosis, dry eye disease and thrombosis. On the horizon are novel treatments for cardiovascular diseases, inflammatory diseases and neurodegeneration.

Published by Elsevier Ltd.

Figures

Figure 1

Nucleotides derivatives that have been useful as agonists in the study of the P2Y receptors.

Figure 2

Nucleotides and nonnucleotides that have been useful antagonists in the study of P2Y receptors. A) Antagonists of the Gq-coupled P2Y1-like subfamily. B) Antagonists of the Gi-coupled P2Y12-like subfamily.

Figure 2

Nucleotides and nonnucleotides that have been useful antagonists in the study of P2Y receptors. A) Antagonists of the Gq-coupled P2Y1-like subfamily. B) Antagonists of the Gi-coupled P2Y12-like subfamily.