Department for Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Department for Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Trends Pharmacol Sci. 2021 Dec;42(12):1035-1050. doi: 10.1016/j.tips.2021.09.008. Epub 2021 Oct 18.
Tissue acidification is associated with a variety of disease states, and acid-sensing ion channels (ASICs) that can sense changes in pH have gained traction as possible pharmaceutical targets. An array of modulators, ranging from small molecules to large biopharmaceuticals, are known to inhibit ASICs. Here, we summarize recent insights from animal studies to assess the therapeutic potential of ASICs in disorders such as ischemic stroke, various pain-related processes, anxiety, and cardiac pathologies. We also review the factors that present a challenge in the pharmacological targeting of ASICs, and which need to be taken into careful consideration when developing potent and selective modulators in the future.
组织酸化与多种疾病状态有关，能够感知 pH 值变化的酸敏离子通道 (ASICs) 已成为可能的药物靶点。一系列的调节剂，从小分子到大生物制药，都被已知可以抑制 ASICs。在这里，我们总结了来自动物研究的最新见解，以评估 ASICs 在缺血性中风、各种与疼痛相关的过程、焦虑和心脏病理等疾病中的治疗潜力。我们还回顾了在药理学靶向 ASICs 时面临的挑战因素，以及在未来开发有效和选择性调节剂时需要仔细考虑的因素。
