Targeting P2Y14 Receptor in Inflammatory and Metabolic Diseases: from Pathophysiology to Therapeutic Inhibitors.

The P2Y14 receptor (P2Y14R) is a G protein-coupled receptor (GPCR) that can be activated by the extracellular nucleotide uridine diphosphate glucose (UDPG). It performs crucial regulatory roles in diverse pathophysiological contexts, such as immune modulation, inflammatory responses, tumor progression, and metabolic disorders. Therefore, it represents a highly attractive therapeutic target. This review elucidates the signal transduction mechanism of P2Y14R and its pathological functions in conditions such as gouty arthritis (GA) and neuropathic pain (NP). Meanwhile, P2Y14R inhibitors based on multiple drug discovery strategies are also comprehensively summarized. Furthermore, this review analyzes the key challenges currently faced in inhibitors research and development. By integrating the latest reported crystal structure of P2Y14R, it looks forward to the prospects of precise drug design based on structure and clinical translation. This provides a theoretical basis and innovative direction for the future development of P2Y14R-targeted therapeutic drugs.