蛋白质-蛋白质相互作用调节剂：进展、成果与尚存挑战
Protein-protein interaction modulators: advances, successes and remaining challenges.
作者信息
Mabonga Lloyd, Kappo Abidemi Paul
机构信息
Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South Africa.
出版信息
Biophys Rev. 2019 Aug;11(4):559-581. doi: 10.1007/s12551-019-00570-x. Epub 2019 Jul 12.
Abstract
Modulating disease-relevant protein-protein interactions (PPIs) using small-molecule inhibitors is a quite indispensable diagnostic and therapeutic strategy in averting pathophysiological cues and disease progression. Over the years, targeting intracellular PPIs as drug design targets has been a challenging task owing to their highly dynamic and expansive interfacial areas (flat, featureless and relatively large). However, advances in PPI-focused drug discovery technology have been reported and a few drugs are already on the market, with some potential drug-like candidates already in clinical trials. In this article, we review the advances, successes and remaining challenges in the application of small molecules as valuable PPI modulators in disease diagnosis and therapeutics.
摘要
使用小分子抑制剂调节与疾病相关的蛋白质-蛋白质相互作用（PPI）是避免病理生理线索和疾病进展中一项不可或缺的诊断和治疗策略。多年来，将细胞内PPI作为药物设计靶点一直是一项具有挑战性的任务，因为它们具有高度动态和广阔的界面区域（平坦、无特征且相对较大）。然而，已有关于以PPI为重点的药物发现技术的进展报道，并且一些药物已经上市，一些潜在的类药物候选物已进入临床试验阶段。在本文中，我们综述了小分子作为有价值的PPI调节剂在疾病诊断和治疗中的应用进展、成功之处及尚存的挑战。
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