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Oxidative Medicine and Cellular Longevity
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Oxidative Medicine and Cellular Longevity
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2019
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Article
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Tab 1
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Review Article
Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development
Table 1
Selected electrophilic activators of NRF2 under clinical development.
Compound
Type
Mechanism of action
Disease
Clinical trial
ClinicalTrials.gov identifier
Bardoxolone-methyl (CDDO-Me)
Synthetic triterpenoids
Electrophilic modification of KEAP1-Cys-151
Diabetic nephropathy
Phase II
NCT00811889
IgA nephropathy
CKD associated with type 1 diabetes
Focal segmental glomerulosclerosis
Autosomal dominant polycystic kidney
Phase II
NCT03366337
Chronic kidney disease
Type 2 diabetes
Diabetic nephropathy
Phase III
NCT01351675
Liver disease
Phase I/II
NCT00550849
Hepatic impairment
Healthy
Phase I
NCT01563562
Advanced solid tumors lymphoid malignancies
Phase I
NCT00529438
NCT00508807
Alport syndrome
Phase II/III cardinal
NCT03019185
Pulmonary hypertension
Phase III RANGER
NCT03068130
Pulmonary arterial hypertension
Phase III
NCT02657356
Renal insufficiency, chronic
Diabetes mellitus, type 2
Phase II
NCT01053936
RTA-408 (omaveloxolone)
Synthetic triterpenoids
Electrophilic modification of KEAP1-Cys-151
Mitochondrial myopathy
Phase II
NCT02255422
Friedreich’s ataxia
Phase II
NCT02255435
Inflammation and pain following ocular surgery
Phase II
NCT02065375
Corneal endothelial cell loss
Ocular pain
Ocular inflammation
Cataract surgery
Phase II
NCT02128113
Melanoma
Phase I/II
NCT02259231
Breast cancer
Phase II
NCT02142959
Dimethyl fumarate
Fumaric acid ester
Electrophilic modification of KEAP1-Cys-151
Multiple sclerosis
Approved
Psoriasis
Approved
Rheumatoid arthritis
Phase II
NCT00810836
Adult brain glioblastoma
Phase I
NCT02337426
Cutaneous T cell lymphoma
Phase II
NCT02546440
Obstructive sleep apnea
Phase II
NCT02438137
Chronic lymphocytic leukemia
Small lymphocytic lymphoma
Phase I
NCT02784834
ALKS-8700
Fumaric acid ester (MMF-derivate)
Electrophilic modification of KEAP1-Cys-151
Multiple sclerosis
Phase III
NCT02634307
Oltipraz
Organosulfur compound
Electrophilic modification of KEAP1-Cys-151
Nonalcoholic steatohepatitis
Phase III
NCT02068339
Schistosomiasis
Approved
Lung cancer
Phase I
NCT00006457
Ursodiol
Biliary acid
Electrophilic modification of KEAP1-Cys-151
Cholestasis
Phase II/III
NCT00846963
Diarrhea
Phase IV
NCT02748616
Cholelithiasis
Phase III
NCT02721862
Primary biliary cirrhosis
Phase IV
NCT01510860
Barrett esophagus
Low-grade dysplasia
Phase II
NCT01097304
Chronic hepatitis C
Phase III
NCT00200343
Type 2 diabetes mellitus
Phase II
NCT02033876
Sulforaphane
Isothiocyanate
Electrophilic modification of KEAP1-Cys-151
Schizophrenia
Phase II/III
NCT02880462
Phase II
NCT02810964
Phase II
NCT01716858
COPD
Phase II
NCT01335971
Atopic asthmatics
Phase I
NCT01845493
Autism spectrum disorder
Phase II
NCT01474993
Phase II
NCT02909959
Phase II
NCT02677051
Phase II
NCT02654743
Phase I/II
NCT02561481
Healthy
Phase I
NCT01008826
Phase I
NCT02023931
Melanoma
Phase I
NCT01568996
Asthma
Phase I
NCT01845493
Phase I/II
NCT01183923
Prostate cancer
Phase II
NCT01228084
Breast cancer
Phase II
NCT00843167
Lung cancer
Phase II
NCT03232138
Environmental carcinogenesis
Phase II
NCT01437501
Alcohol sensitivity
Phase II
NCT01845220
Aging
Phase II
NCT03126539
Rhinitis, allergic
Phase II
NCT02885025
Helicobacter pylori infection
Phase IV
NCT03220542
Diabetes mellitus, noninsulin-dependent
Phase II
NCT02801448
Sulforadex (SFX-01)
Sulforaphane/alpha-cyclodextrin complex
Electrophilic modification of KEAP1-Cys-151
Subarachnoid haemorrhage
Phase II
NCT02614742
Breast neoplasm
Phase I/II
NCT02970682
Prostate cancer
Phase I
NCT02055716
NCT01948362
ITH12674
Melatonin-sulforaphane hybrid
Electrophilic modification of KEAP1-Cys-151
Brain ischemia
Preclinical PK
No clinical trials available
Curcumin
Stilbene
Electrophilic modification of KEAP1-Cys-151
Type 2 diabetes
Prediabetes
Insulin resistance
Cardiovascular risk
Phase IV
NCT01052025
Schizophrenia
Cognition
Psychosis
Phase I/II
NCT02104752
Acute kidney injury
Abdominal aortic aneurysm
Phase II/III
NCT01225094
Chronic kidney diseases
Diabetes mellitus, type 2
Polymorphism
Phase II/III
NCT03262363
Alzheimer’s disease
Phase I/II
NCT00164749
Neoplasms
Phase II
NCT02944578
Crohn’s disease
Phase III
NCT02255370
Chronic schizophrenia
Phase IV
NCT02298985
Mild cognitive impairment
Phase II
NCT01811381
Prostate cancer
Phase III
NCT02064673
Major depression
Phase IV
NCT01750359
Resveratrol
(
E
)-Stilbene derivate
Electrophilic modification of KEAP1-Cys-151
Type 2 diabetes
Phase I
NCT01677611
Colon cancer
Phase I
NCT00256334
COPD
N/A
NCT02245932
Friedreich ataxia
Phase I/II
NCT01339884
Nonalcoholic fatty liver
Phase II/III
NCT02030977
Nonischemic cardiomyopathy
Phase III
NCT01914081
Endometriosis
Phase IV
NCT02475564
Chronic renal insufficiency
Phase III
NCT02433925
Metabolic syndrome X
Phase II
NCT02114892
Chronic subclinical inflammation
Redox status
Phase III
NCT01492114
Alzheimer’s disease
Phase II
NCT01504854
Phase III
NCT00743743
Huntington disease
Phase III
NCT02336633
CXA-10
Nitro-fatty acid (NFA)
Electrophilic modification of KEAP1-Cys-273 and Cys-288
Acute kidney injury
Phase I
NCT02248051
Pulmonary arterial hypertension (PAH)
Phase II
NCT03449524
Primary focal segmental glomerulosclerosis (FSGS)
Phase II
NCT03422510