Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists

doi:10.1021/acs.jmedchem.0c01378

	Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists
	Chen, Lin-Hai 1; Zhang, Qing 2; Xie, Xin 2; Nan, Fa-Jun 1,3
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2020-12-24
卷号	63 期号:24 页码:15399-15409
ISSN号	0022-2623
DOI	10.1021/acs.jmedchem.0c01378
通讯作者	Xie, Xin(xxie@simm.ac.cn) ; Nan, Fa-Jun(fjnan@simm.ac.cn)
英文摘要	Since the discovery of medium-chain fatty acids as GPR84 ligands, significant advancements have been made in the development of GPR84 agonists and antagonists. Most agonists have lipid-like structures except for 3,3'-diindolylmethane (DIM), which acts as an allosteric agonist. GPR84 activation in macrophages leads to increased cytokine secretion, chemotaxis, and phagocytosis, revealing the proinflammatory role of GPR84 associated with various inflammatory responses. Three GPR84 antagonists (S)-2-((1,4-dioxan-2-yl)methoxy)-9-(cyclopropylethynyl)-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one (GLPG1205), sodium 2-(3-pentylphenyl)acetate (PBI-4050), and sodium 2-(3,5-dipentylphenyl)acetate (PBI-4547) have displayed therapeutic effects in animal models of several inflammatory and fibrotic diseases and are being evaluated in clinical studies. Although GLPG1205 has failed in a clinical trial for ulcerative colitis, it is undergoing another phase II clinical study for idiopathic pulmonary fibrosis. Further studies are needed to resolve the GPR84 structure, identify more endogenous ligands, elucidate their physiological and pathological roles, and fulfill the therapeutic potential of GPR84 antagonists and agonists.
资助项目	Personalized Medicines.Molecular Signature-Based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020229] ; National Natural Science Foundation of China[81730099] ; National Natural Science Foundation of China[22077132] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002002] ; Shanghai Science and Technology Development Funds[20ZR1471200] ; Shanghai Science and Technology Development Funds[20S11903200] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2017329]
WOS关键词	FREE FATTY-ACIDS ; EXPRESSION ; SECRETION ; DISCOVERY ; CHILDREN ; LIGANDS ; EMBELIN ; PLASMA ; CELLS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000603401900017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296038]
专题	中国科学院上海药物研究所
通讯作者	Xie, Xin; Nan, Fa-Jun
作者单位	1.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Yantai Inst Mat Med, Yantai 264000, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Chen, Lin-Hai,Zhang, Qing,Xie, Xin,et al. Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists[J]. JOURNAL OF MEDICINAL CHEMISTRY,2020,63(24):15399-15409.
APA	Chen, Lin-Hai,Zhang, Qing,Xie, Xin,&Nan, Fa-Jun.(2020).Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists.JOURNAL OF MEDICINAL CHEMISTRY,63(24),15399-15409.
MLA	Chen, Lin-Hai,et al."Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists".JOURNAL OF MEDICINAL CHEMISTRY 63.24(2020):15399-15409.