Abstract
Bromodomains, small protein modules that recognize acetylated lysine on histones, play a significant role in the epigenome, where they function as "readers" that ultimately determine the functional outcome of the post-translational modification. Because the initial discovery of selective BET inhibitors have helped define the role of that protein family in oncology and inflammation, BET bromodomains have continued to garner the most attention of any other bromodomain. More recently, non-BET bromodomain inhibitors that are potent and selective have been disclosed for ATAD2, CBP, BRD7/9, BRPF, BRPF/TRIM24, CECR2, SMARCA4, and BAZ2A/B. Such novel inhibitors can be used to probe the physiological function of these non-BET bromodomains and further understanding of their role in certain disease states. Here, we provide an update to the progress in identifying selective bromodomain inhibitors and their use as biological tools, as well as our perspective on the field.
MeSH 主题词
ATPases Associated with Diverse Cellular Activities
Acetylation/drug effects
Adaptor Proteins, Signal Transducing/antagonists & inhibitors,metabolism
Adenosine Triphosphatases/antagonists & inhibitors,metabolism
Animals
Antigens, Nuclear/metabolism
CREB-Binding Protein/antagonists & inhibitors,metabolism
Carrier Proteins/antagonists & inhibitors,metabolism
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone/antagonists & inhibitors,metabolism
DNA Helicases/antagonists & inhibitors,metabolism
DNA-Binding Proteins/antagonists & inhibitors,metabolism
Drug Discovery/methods
Histones/metabolism
Humans
Lysine/metabolism
Models, Molecular
Nerve Tissue Proteins/antagonists & inhibitors,metabolism
Nuclear Proteins/antagonists & inhibitors,metabolism
Protein Processing, Post-Translational/drug effects
Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism
RNA-Binding Proteins/antagonists & inhibitors,metabolism
Small Molecule Libraries/chemistry,pharmacology
Transcription Factors/antagonists & inhibitors,metabolism
化学物质
Adaptor Proteins, Signal Transducing
Antigens, Nuclear
BAZ2A protein, human
BRD2 protein, human
BRD3 protein, human
BRD4 protein, human
BRD7 protein, human
BRD9 protein, human
BRDT protein, human
BRPF1 protein, human
Carrier Proteins
Cecr2 protein, human
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Histones
Nerve Tissue Proteins
Nuclear Proteins
RNA-Binding Proteins
Small Molecule Libraries
TRIM24 protein, human
Transcription Factors
fetal Alzheimer antigen
CREB-Binding Protein
CREBBP protein, human
Protein Serine-Threonine Kinases
Adenosine Triphosphatases
SMARCA4 protein, human
ATAD2 protein, human
ATPases Associated with Diverse Cellular Activities
DNA Helicases
Lysine
作者与单位
共 6 位作者，点击展开单位 / ORCID
Romero F Anthony
Discovery Chemistry, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, United States.
Taylor Alexander M
Constellation Pharmaceuticals, Inc. 215 First Street, Suite 200, Cambridge, Massachusetts 02142, United States.
Crawford Terry D
Discovery Chemistry, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, United States.
Tsui Vickie
Discovery Chemistry, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, United States.
Côté Alexandre
Constellation Pharmaceuticals, Inc. 215 First Street, Suite 200, Cambridge, Massachusetts 02142, United States.
Magnuson Steven
Discovery Chemistry, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, United States.
