hERG is best known as a primary anti-target, the inhibition of which is responsible for serious side effects. A renewed interest in hERG as a desired target, especially in oncology, was sparked because of its role in cellular proliferation and apoptosis. In this study, we survey the most recent advances regarding hERG by focusing on SAR in the attempt to elucidate, at a molecular level, off-target and on-target actions of potential hERG binders, which are highly promiscuous and largely varying in structure. Understanding the rationale behind hERG interactions and the molecular determinants of hERG activity is a real challenge and comprehension of this is of the utmost importance to prioritize compounds in early stages of drug discovery and to minimize cardiotoxicity attrition in preclinical and clinical studies.

中文翻译：

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与人类醚相关的钾通道：探索SAR改善药物设计。

hERG最著名的是主要的抗靶标，其抑制作用导致严重的副作用。由于其在细胞增殖和凋亡中的作用，引起了人们对hERG作为理想靶标，尤其是肿瘤学的新兴趣。在这项研究中，我们通过关注SAR来研究有关hERG的最新进展，以在分子水平上阐明潜在的hERG结合剂的脱靶和脱靶作用，这些靶物高度混杂且结构差异很大。理解hERG相互作用背后的基本原理以及hERG活性的分子决定因素是一项真正的挑战，对此的理解对于在药物发现的早期阶段确定化合物的优先级并在临床前和临床研究中最大程度地减少心脏毒性的减少是至关重要的。