BET proteins: Biological functions and therapeutic interventions

IF 12 1区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacology & Therapeutics Pub Date : 2023-03-01 DOI:10.1016/j.pharmthera.2023.108354

Jiawei Guo , Qingquan Zheng , Yong Peng

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引用次数: 2

Abstract

Bromodomain and extra-terminal (BET) family member proteins (BRD2, BRD3, BRD4 and BRDT) play a pivotal role in interpreting the epigenetic information of histone Kac modification, thus controlling gene expression, remodeling chromatin structures and avoid replicative stress-induced DNA damages. Abnormal activation of BET proteins is tightly correlated to various human diseases, including cancer. Therefore, BET bromodomain inhibitors (BBIs) were considered as promising therapeutics to treat BET-related diseases, raising >70 clinical trials in the past decades. Despite preliminary effects achieved, drug resistance and adverse events represent two major challenges for current BBIs development. In this review, we will introduce the biological functions of BET proteins in both physiological and pathological conditions; and summarize the progress in current BBI drug development. Moreover, we will also discuss the major challenges in the front of BET inhibitor development and provide rational strategies to overcome these obstacles.

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BET蛋白:生物学功能和治疗干预

溴域和外端(BET)家族成员蛋白(BRD2, BRD3, BRD4和BRDT)在解释组蛋白Kac修饰的表观遗传信息，从而控制基因表达，重塑染色质结构，避免复制应激诱导的DNA损伤中发挥关键作用。BET蛋白的异常激活与包括癌症在内的多种人类疾病密切相关。因此，BET溴域抑制剂(BBIs)被认为是治疗BET相关疾病的有希望的治疗方法，在过去的几十年里进行了70多项临床试验。尽管取得了初步效果，但耐药和不良事件是目前BBIs发展的两大挑战。本文将介绍BET蛋白在生理和病理条件下的生物学功能;总结了目前BBI药物的开发进展。此外，我们还将讨论BET抑制剂开发面临的主要挑战，并提供克服这些障碍的合理策略。

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

Pharmacology & Therapeutics 医学-药学

CiteScore

23.00

自引率

0.70%

发文量

222

审稿时长

90 days

期刊介绍： Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.