Recent progress on the discovery of P2Y14 receptor antagonists

Abstract

The P2Y₁₄ receptor (P2Y₁₄R), a G protein-coupled receptor (GPCR), is activated by extracellular nucleotides. P2Y₁₄R is involved in inflammatory, diabetes, immune processes and other related complications, and is therefore an attractive therapeutic target. As the three-dimensional structure of the P2Y₁₄R has not yet been elucidated, homology modeling based on the crystallography of the closely related P2Y₁₂R have been used in the structure-based design of P2Y₁₄R ligands. Several P2Y₁₄R antagonists with excellent potency and high subtype-selectivity have been discovered in recent years. In this review, development of novel small molecules as antagonists of P2Y₁₄R was described.

Keywords: Antagonist; G protein-coupled receptor; P2Y(14) receptor; PPTN.