TY - JOUR
T1 - Bromodomain-containing protein 4 (BRD4)
T2 - a key player in inflammatory bowel disease and potential to inspire epigenetic therapeutics
AU - Ma, Zonghui
AU - Bolinger, Andrew A.
AU - Zhou, Jia
AU - Tian, Bing
N1 - Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Bromodomain-containing protein 4 (BRD4)
KW - Crohn’s disease (CD)
KW - anti-inflammatory therapy
KW - drug target
KW - epigenetics
KW - inflammatory bowel disease (IBD)
KW - nuclear factor-κB (nfκb)
KW - ulcerative colitis (UC)
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U2 - 10.1080/14728222.2023.2175317
DO - 10.1080/14728222.2023.2175317
M3 - Article
C2 - 36710583
AN - SCOPUS:85147682764
SN - 1472-8222
VL - 27
SP - 1
EP - 7
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 1
ER -