炎症性肠病(IBD)是一种让人严重受苦的慢性炎症性疾病，在全球范围内有日益增多的患病率。表观遗传调控因子溴域蛋白4(BRD4)在调控与IBD有关的炎症因子网络的基因表达中发挥着关键作用。作为前景广阔的治疗靶点，BRD4也紧密联系着许多其他疾病，比如呼吸道炎症和纤维化、癌症、传染病和中枢神经系统疾病。本综述简要总结了BRD4在IBD发病机制中的重要作用以及发展溴域和额外末端域(BET)抑制剂的目前临床状况。同时也讨论了定向BRD4抑制剂作为潜在IBD药物的挑战、机遇和未来方向。采用高效、特异的BRD4抑制剂对BRD4靶点进行定向治疗，或许可以为IBD患者提供新型有效的治疗方案，特别是对于那些难以耐受抗TNF-α治疗以及IBD相关的纤维化的患者。开发高度特异的IBD用BRD4抑制剂，将有望消除大部分目前所有的通用BET/BRD4抑制剂的缺点，比如靶向效果差、口服生物利用度低和肠道黏膜吸收性差。采用新型策略，疗效互补的治疗、基于BRD4的双靶点抑制剂和蛋白酶分解靶向融合物(简称PROTACs)，也有可能在IBD治疗中减轻副作用并克服药物耐药。

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.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.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.