P2Y6R: A Promising New Target in Inflammatory Diseases and Advances in its Antagonists

Yuanhui Wang; Yuanyuan Pei; Yongfang Yao; Weyland Cheng; Yinchao Li; Yongtao Duan

doi:10.2174/0929867329666220614100218

P2Y₆R: A Promising New Target in Inflammatory Diseases and Advances in its Antagonists

Curr Med Chem. 2023;30(19):2209-2224. doi: 10.2174/0929867329666220614100218.

Authors

Yuanhui Wang^{1

2}, Yuanyuan Pei^{1

2}, Yongfang Yao^{2

3}, Weyland Cheng¹, Yinchao Li², Yongtao Duan¹

Affiliations

¹ Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou 450018, China.
² School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
³ Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.

PMID: 35702786
DOI: 10.2174/0929867329666220614100218

Abstract

P2Y receptors (P2YRs) are G protein-coupled receptors that are activated by extracellular nucleotides. The P2Y6 receptor (P2Y₆R) is specifically activated by UDP, causing PKC activation and intracellular calcium ion release through the PLC pathway. Based on receptor tissue distribution and related pathways, several studies have reported that P2Y₆R plays a physiological role in mediating inflammation, which suggests that P2Y₆R could be a promising molecular target for the treatment of inflammatory diseases. In the past ten years, several P2Y₆R antagonists have been discovered as new therapeutic strategies for inflammatory diseases. In this article, we systematically summarize the role of P2Y₆R in inflammation and highlight the anti-inflammatory mechanism of a key P2Y₆R antagonist, MRS2578. Insight into recent progress on the discovery of P2Y₆R antagonists is also discussed.

Keywords: P2Y₆R; antagonist; inflammation; mechanism; nucleotides; therapeutic strategies.

MeSH terms

Humans
Inflammation* / drug therapy