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General Review Article

从对p97功能机制的结构研究中洞察p97靶向小分子的设计

卷 27, 期 2, 2020

页: [298 - 316] 页: 19

弟呕挨: 10.2174/0929867326666191004162411

价格: $65

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摘要

p97，也被称为含有球蛋白的蛋白或CDC48，是在真核生物中高度保守的AAA+蛋白家族中的一员。它与体内各种辅助因子结合，发挥其蛋白展开功能，并参与DNA修复、亚细胞膜蛋白降解、蛋白质量控制等过程。其功能障碍可导致多种疾病，如包涵体肌病、伴骨性和/或额颞叶痴呆的Paget s病、肌萎缩性脊髓侧索硬化症等。近年来，许多小分子抑制剂被用于p97，包括双(二乙基二硫代氨基甲酸酯)铜和CB-5083，它们进入了临床试验的第一阶段，但失败了。p97药物设计的一个瓶颈是其分子机制尚不清楚。本文综述了近年来对p97分子机制的研究，以期为设计新一代靶向p97的小分子提供参考。

关键词: p97/VCP/CDC48

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