Therapeutic targeting of "undruggable" MYC.

IF 13.1 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2022-01-01 Epub Date: 2021-12-20 DOI:10.1016/j.ebiom.2021.103756

Victor Llombart, Marc R Mansour

引用次数: 0

Abstract

c-MYC controls global gene expression and regulates cell proliferation, cell differentiation, cell cycle, metabolism and apoptosis. According to some estimates, MYC is dysregulated in ≈70% of human cancers and strong evidence implicates aberrantly expressed MYC in both tumor initiation and maintenance. In vivo studies show that MYC inhibition elicits a prominent anti-proliferative effect and sustained tumor regression while any alteration on healthy tissue remains reversible. This opens an exploitable window for treatment that makes MYC one of the most appealing therapeutic targets for cancer drug development. This review describes the main functional and structural features of the protein structure of MYC and provides a general overview of the most relevant or recently identified interactors that modulate MYC oncogenic activity. This review also summarizes the different approaches aiming to abrogate MYC oncogenic function, with a particular focus on the prototype inhibitors designed for the direct and indirect targeting of MYC.

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针对 "不可救药 "的 MYC 的治疗。

c-MYC 控制全局基因表达，调节细胞增殖、细胞分化、细胞周期、新陈代谢和细胞凋亡。据估计，MYC 在 70% 的人类癌症中失调，有确凿证据表明，异常表达的 MYC 与肿瘤的发生和维持有关。体内研究表明，抑制 MYC 可产生显著的抗增殖作用和持续的肿瘤消退，而对健康组织的任何改变都是可逆的。这为治疗打开了一扇可利用的窗口，使 MYC 成为癌症药物开发中最具吸引力的治疗靶点之一。本综述描述了 MYC 蛋白结构的主要功能和结构特征，并概述了最相关或最近发现的可调节 MYC 致癌活性的相互作用因子。本综述还总结了旨在消减 MYC 致癌功能的不同方法，尤其关注为直接或间接靶向 MYC 而设计的原型抑制剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.