Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence.
Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence.
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DOI：
10.1007/s00109-021-02163-2
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Pereira SA
中科院分区：
文献类型：
--
作者：
Coelho NR;Pimpão AB;Correia MJ;Rodrigues TC;Monteiro EC;Morello J;Pereira SA
芳烃受体（AHR）是一种配体激活的转录因子，可被来自环境和微生物群以及宿主代谢的结构多样性化合物激活。越来越多的证据表明，AHR经典途径的调节发生在几种慢性疾病中，其废除可能对代谢和炎症病理过程具有临床意义。然而，大多数关于AHR-CYP 1A 1轴药理学消除的证据都是在体外报告的，因此，需要对体内研究进行指导。在这篇综述中，我们涵盖了最先进的AHR拮抗剂和CYP 1A 1抑制剂在不同的体内啮齿动物（小鼠或大鼠）疾病模型的药效学和药代动力学特性。这篇综述将作为那些研究人员拥抱这一新兴的治疗领域针对AHR的路线图。此外，这是一个及时的机会，因为第一个AHR拮抗剂最近已进入药物开发的临床阶段。
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that can be activated by structurally diverse compounds arising from the environment and the microbiota and host metabolism. Expanding evidence has been shown that the modulation of the canonical pathway of AHR occurs during several chronic diseases and that its abrogation might be of clinical interest for metabolic and inflammatory pathological processes. However, most of the evidence on the pharmacological abrogation of the AHR-CYP1A1 axis has been reported in vitro, and therefore, guidance for in vivo studies is needed. In this review, we cover the state-of-the-art of the pharmacodynamic and pharmacokinetic properties of AHR antagonists and CYP1A1 inhibitors in different in vivo rodent (mouse or rat) models of disease. This review will serve as a road map for those researchers embracing this emerging therapeutic area targeting the AHR. Moreover, it is a timely opportunity as the first AHR antagonists have recently entered the clinical stage of drug development.
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