REVIEWDiscovery of direct inhibitors of Keap1–Nrf2 protein–protein interaction as potential therapeutic and preventive agents
Under a Creative Commons license
open access
Graphical abstract
The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress. Non-covalent direct inhibition of the Keap1–Nrf2 protein–protein interaction (PPI) has become an important approach to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions.
Abbreviations
1O2
singlet oxygen
AD
Alzheimer׳s disease
ARE
antioxidant response element
Bach1
BTB and CNC homology 1
BTB
broad complex, tramtrack and bric-a-brac
CBP
cAMP response element binding (CREB) protein
CDDO-Me
bardoxolone methyl
COPD
chronic obstructive pulmonary disease
CTR
C-terminal region
CVD
cardiovascular disease
DGR
double glycine repeats
FITC
flurescein isothiocyanate
FP
fluorescence polarization
GCL
glutamate-cysteine ligase
GPx
glutathione peroxidase
GST
glutathione S-transferase
H2O2
hydrogen peroxide
HO-1
heme-oxygenase-1
HTS
high-throughput screening
IBS
inflammatory bowel disease
IVR
intervening region
Keap1
Kelch-like ECH-associated protein 1
MD
molecular dynamics
NMR
.
NO
nitric oxide
NQO1
NAD(P)H quinone oxidoreductase I
Nrf2
nuclear factor erythroid 2–related factor 2
NTR
N-terminal region
superoxide, OH·, hydroxyl radical
peroxynitrate
PD
Parkinson׳s disease
PPI
protein–protein interaction
RNS
reactive nitrogen species
ROS
reactive oxygen species
SOD
superoxide dismutase
SPR
surface plasmon resonance
STZ
streptozotocin
THIQ
tetrahydroisoquinoline
TRX
thioredoxin
vitamin C
ascorbate
vitamin E
tocopherols
KEY WORDS
Oxidative stress
Keap1
Nrf2
Direct inhibitors of protein–protein interaction
High throughput screening assays
Structure–activity relationships
X-ray crystallography
Cited by (0)
Peer review under responsibility of Institute of Materia Medica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association.
Copyright © 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.