Recent progress on the discovery of P2Y14 receptor antagonists.

The P2Y 14 receptor (P2Y 14 R), a G protein-coupled receptor (GPCR), is activated by extracellular nucleotides. P2Y 14 R 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 P2Y 14 R has not yet been elucidated, homology modeling based on the crystallography of the closely related P2Y 12 R have been used in the structure-based design of P2Y 14 R ligands. Several P2Y 14 R 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 P2Y 14 R was described. UDP non-competitive P2Y 14 R antagonist. UDP competitive P2Y 14 R antagonists. Image 1 • Development of novel small molecules as antagonists of P2Y 14 R was reviewed. • Developing drug-like UDP competitive P2Y 14 R antagonists was mentioned. • UDP non-competitive P2Y 14 R antagonist avoiding side-effects was suggested. [ABSTRACT FROM AUTHOR]