Bromodomain inhibitors and therapeutic applications

• Published in: Current opinion in chemical biology Vol. 75; p. 102323
• Main Authors: Gajjela, Bharath Kumar, Zhou, Ming-Ming
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2023
• Subjects: BET proteins; Bromodomain; Bromodomain inhibitors; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Cycle Proteins - therapeutic use; Chromatin; Drug discovery; Gene transcription; Histones - metabolism; Humans; Neoplasms - metabolism; Nuclear Proteins - metabolism; Transcription Factors - metabolism; BET proteins; Bromodomain; Drug discovery; Bromodomain inhibitors; Gene transcription
• ISSN: 1367-5931; 1879-0402; 1879-0402
• DOI: 10.1016/j.cbpa.2023.102323

The bromodomain acts to recognize acetylated lysine in histones and transcription proteins and plays a fundamental role in chromatin-based cellular processes including gene transcription and chromatin remodeling. Many bromodomain proteins, particularly the bromodomain and extra terminal domain (BET) protein BRD4 have been implicated in cancers and inflammatory disorders and recognized as attractive drug targets. Although clinical studies of many BET bromodomain inhibitors have made substantial progress toward harnessing the therapeutic potential of targeting the bromodomain proteins, the development of this new class of epigenetic drugs is met with challenges, especially on-target dose-limiting toxicity. In this review, we highlight the current development of new-generation small molecule inhibitors for the BET and non-BET bromodomain proteins and discuss the research strategies used to target different bromodomain proteins for a wide array of human diseases including cancers and inflammatory disorders.