Review Article

通过马努霉素相关天然产物抑制"无药"RAS/法呢基转移酶(FTase)癌症靶标

卷 29, 期 2, 2022

发表于: 15 March, 2021

页: [189 - 211] 页: 23

弟呕挨: 10.2174/0929867328666210315123848

价格: $65

摘要

癌症是一种不受控制的细胞生长,可以产生不同类型的癌症,其中这些在面对药物治疗时也会呈现出不同的行为。这些癌症的类型存在于三类癌症之一,白血病(也称为淋巴瘤),癌和肉瘤。一般来说,癌症的发病机制与三种基因突变有关,其中可能来自癌基因,肿瘤抑制基因和/或负责调节DNA复制的基因。术语"无药可药"通常与设计特定靶标的药物的难度有关,例如MYC,MYB,NF-κB和RAS家族的蛋白质。这最后一种蛋白质包括140多种蛋白质,这些蛋白质占人类癌症突变的30%。此外,在人类细胞中转录了三个ras基因,称为H-,K-和N-ras癌基因。尽管如此,RAS蛋白(法呢基转移酶(FTase)和香叶基香叶基转移酶(GGTase)酶)在真核生物细胞的翻译后修饰中执行基本步骤,例如(1)C端四肽CAAX处半胱氨酸残基的法呢基化;(2)三个C端AAX寡肽的蛋白水解裂解;(3)羧甲基化新的C端预聚半胱氨酸。因此,抑制这种无法药用的RAS家族蛋白质被认为是设计新的抗癌剂的有希望的替代方案,因为它们负责许多类型的人类癌症。然后,马努霉素A(从细小链霉菌Tu64中获得)及其类似物(环氧喹诺核心,有或没有其南部和东部侧链;和二羟基环己烯酮核心)被描述为有前途的FTase抑制剂,这已经证明了它们对几种类型的癌症的益处。本文全面介绍了癌症及其与RAS蛋白的关系,并详细讨论了半胱氨酸残基的孕育机制。在后部,描述了涉及马努霉素相关化合物的研究,显示了一些合成途径,用于获得它们并将这些天然产物用于单一疗法或与其他抗癌药物的联合疗法。

关键词: Ras家族,马努霉素A,明日霉素,LL-C10037α,法呢基转移酶,香叶基香叶基转移酶。

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