Systematic synthesis of novel phosphoglycolipid analogues as potential agonists of GPR55

被引:4
|
作者
Abe, Junpei [1 ]
Guy, Adam T. [2 ]
Ding, Feiqing [3 ]
Greimel, Peter [2 ]
Hirabayashi, Yoshio [4 ]
Kamiguchi, Hiroyuki [2 ]
Ito, Yukishige [1 ,4 ]
机构
[1] Osaka Univ, Grad Sch Sci, Toyonaka, Osaka 5600043, Japan
[2] RIKEN, Ctr Brain Res, Wako, Saitama 3510198, Japan
[3] Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Guangzhou 510275, Peoples R China
[4] RIKEN Cluster Pioneering Res, Wako, Saitama 3510198, Japan
关键词
COUPLED RECEPTOR GPR55; CANNABINOID RECEPTOR; SIGNALING PATHWAYS; DRUG DISCOVERY; LYSOPHOSPHATIDYLINOSITOL; IDENTIFICATION; CANCER; LIGAND; CELLS; ISLETS;
D O I
10.1039/d0ob01756f
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Rhodopsin-like G protein-coupled receptor (GPCR) GPR55 is attracting attention as a pharmaceutical target, because of its relationship with various physiological and pathological events. Although GPR55 was initially deorphanized as a cannabinoid receptor, lysophosphatidylinositol (LPI) is now widely perceived to be an endogenous ligand of GPR55. Recently, lysophosphatidyl-beta-d-glucoside (LPGlc) has been found to act on GPR55 to repel dorsal root ganglion (DRG) neurons. In this study, we designed and synthesized various LPGlc analogues having the squaryldiamide group as potential agonists of GPR55. By the axon turning assay, several analogues exhibited similar activities to that of LPGlc. These results will provide valuable information for understanding the mode of action of LPGlc and its analogues and for the discovery of potent and selective antagonists or agonists of GPR55.
引用
收藏
页码:8467 / 8473
页数:7
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