Bromodomain-containing protein 4 (BRD4): a key player in inflammatory bowel disease and potential to inspire epigenetic therapeutics

BRD4 溴尿嘧啶 医学 表观遗传学 炎症性肠病 疾病 生物信息学 免疫学 生物 病理 生物化学 基因
作者
Zonghui Ma,Andrew A. Bolinger,Jia Zhou,Bing Tian
出处
期刊:Expert Opinion on Therapeutic Targets [Informa]
卷期号:27 (1): 1-7 被引量:13
标识
DOI:10.1080/14728222.2023.2175317
摘要

Introduction Inflammatory bowel diseases (IBDs) are debilitating chronic inflammatory disorders with increasing prevalence worldwide. Epigenetic regulator bromodomain-containing protein 4 (BRD4) is critical in controlling gene expression of IBD-associated inflammatory cytokine networks. BRD4 as a promising therapeutic target is also tightly associated with many other diseases, such as airway inflammation and fibrosis, cancers, infectious diseases and central nervous system disorders.Areas covered This review briefly summarized the critical role of BRD4 in the pathogenesis of IBDs and the current clinical landscape of developing bromodomain and extra terminal domain (BET) inhibitors. The challenges and opportunities as well as future directions of targeting BRD4 inhibition for potential IBD medications were also discussed.Expert opinion Targeting BRD4 with potent and specific inhibitors may offer novel effective therapeutics for IBD patients, particularly those who are refractory to anti-TNFα therapy and IBD-related profibrotic. Developing highly specific BRD4 inhibitors for IBD medications may help erase the drawbacks of most current pan-BET/BRD4 inhibitors, such as off-target effects, poor oral bioavailability, and low gut mucosal absorbance. Novel strategies such as combinatorial therapy, BRD4-based dual inhibitors and proteolysis targeting chimeras (PROTACs) may also have great potential to mitigate side effects and overcome drug resistance during IBD treatment.
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