Title:Small-Molecule BET Inhibitors in Clinical and Preclinical Development and Their Therapeutic Potential
Volume: 15
Issue: 8
Author(s): Lei Yu, Zhen Wang, Zhang Zhang, Xiaomei Ren, Xiaoyun Lu and Ke Ding
Affiliation:
Keywords:
Acetyl-lysine (KAc) binding pocket, Bromodomain (BRDs), Bromo and extra-terminal (BET) proteins, Medicinal
implications, Selectivity, Small-molecule inhibitors.
Abstract: Lysine acetylation is a pivotal mechanism in chromatin processes and the
regulation of gene transcription. The acetylated lysine residues of histones are exclusively
recognized by bromodomains (BRDs) known as epigenetic reader. Proteins
containing BRDs undergo a post-translational modification (PTM) with development
of cellular signaling and disease biology. The bromo and extra-terminal (BET) proteins
are the second subfamily, which play important roles in cellular proliferation, cell cycle progression and chromatin
compaction. Recently, a variety of small molecules have been reported to interact with the BET family proteins and accelerate
the validation of BET proteins as druggable targets for treatment of cancers, inflammation and related diseases. In
this review, we will summarize the small-molecule inhibitors in clinical and preclinical studies of the BET family bromodomains
and their medicinal implications.
