Targeting Aryl hydrocarbon receptor for next-generation immunotherapies: Selective modulators (SAhRMs) versus rapidly metabolized ligands (RMAhRLs)

被引:37
作者
Dolciami, Daniela [1 ]
Ballarotto, Marco [1 ]
Gargaro, Marco [2 ]
Carlota Lopez-Cara, Luisa [3 ]
Fallarino, Francesca [2 ]
Macchiarulo, Antonio [1 ]
机构
[1] Univ Perugia, Dept Pharmaceut Sci, Via Liceo 1, I-06123 Perugia, Italy
[2] Univ Perugia, Dept Expt Med, Piazzle Gambuli 1, I-06132 Perugia, Italy
[3] Univ Granada, Fac Pharm, Dept Pharmaceut & Organ Chem, Granada 18010, Spain
关键词
Aryl hydrocarbon receptor; Immunotherapy; RMAhRLs; Selectivity; Specificity; Cancer; POLYCYCLIC AROMATIC-HYDROCARBONS; AH DIOXIN RECEPTOR; GENE-EXPRESSION; BETA-NAPHTHOFLAVONE; CELL-DIFFERENTIATION; BINDING DOMAIN; IN-VIVO; T-CELLS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; FUNCTIONAL SELECTIVITY;
D O I
10.1016/j.ejmech.2019.111842
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Aryl Hydrocarbon Receptor (AhR) constitutes a major network hub of genomic and non-genomic signaling pathways, connecting host's immune cells to environmental factors. It shapes innate and adaptive immune processes to environmental stimuli with species-, cell- and tissue-type dependent specificity, Although an ever increasing number of studies has thrust AhR into the limelight as attractive target for the development of next-generation immunotherapies, concerns exist on potential safety issues associated with small molecule modulation of the receptor. Selective AhR modulators (SAhRMs) and rapidly metabolized AhR ligands (RMAhRLs) are two classes of receptor agonists that are emerging as interesting lead compounds to bypass AhR-related toxicity in favor of therapeutic effects. In this article, we discuss SAhRMs and RMAhRLs reported in literature, covering concepts underlying their definitions, specific binding modes, structure-activity relationships and AhR-mediated functions. (C) 2019 Elsevier Masson SAS. All rights reserved.
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页数:14
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