Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Departments of Nutrition and Food Science and Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Int J Mol Sci. 2020 Sep 11;21(18):6654. doi: 10.3390/ijms21186654.
The aryl hydrocarbon receptor (AhR) was first identified as the intracellular protein that bound and mediated the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and dioxin-like compounds (DLCs). Subsequent studies show that the AhR plays an important role in maintaining cellular homeostasis and in pathophysiology, and there is increasing evidence that the AhR is an important drug target. The AhR binds structurally diverse compounds, including pharmaceuticals, phytochemicals and endogenous biochemicals, some of which may serve as endogenous ligands. Classification of DLCs and non-DLCs based on their persistence (metabolism), toxicities, binding to wild-type/mutant AhR and structural similarities have been reported. This review provides data suggesting that ligands for the AhR are selective AhR modulators (SAhRMs) that exhibit tissue/cell-specific AhR agonist and antagonist activities, and that their functional diversity is similar to selective receptor modulators that target steroid hormone and other nuclear receptors.
芳香烃受体 (AhR) 最初被鉴定为与 2,3,7,8-四氯二苯并对二恶英 (TCDD，二恶英) 和类似二恶英的化合物 (DLCs) 结合并介导其毒性作用的细胞内蛋白。随后的研究表明，AhR 在维持细胞内稳态和病理生理学方面发挥着重要作用，越来越多的证据表明 AhR 是一个重要的药物靶点。AhR 结合结构多样的化合物，包括药物、植物化学物质和内源性生化物质，其中一些可能作为内源性配体。已报道根据其持久性 (代谢)、毒性、与野生型/突变型 AhR 的结合以及结构相似性对 DLCs 和非 DLCs 进行分类。这篇综述提供的数据表明，AhR 的配体是选择性 AhR 调节剂 (SAhRMs)，它们表现出组织/细胞特异性的 AhR 激动剂和拮抗剂活性，其功能多样性与靶向甾体激素和其他核受体的选择性受体调节剂相似。
