Dibenzoylmethane, a minor ingredient in licorice, activates Nrf2 and prevents various cancers and oxidative damage. Dibenzoylmethane, an analog of curcumin, results in dissociation from Keap1 and nuclear translocation of Nrf2[1].
Keap1-Nrf2-IN-5 (compound 1) is a potent Keap1-Nrf2 PPI (Keap1-Nrf2 protein−protein interaction) inhibitor with an IC50 of 4.1 µM, Kd of 3.7 µM[1].
Nrf2-IN-3 (Compound R16) is a Nrf2 inhibitor. Nrf2-IN-3 binds KEAP1 mutants (G333C mKEAP1) and repairs the disrupted KEAP1/NRF2 interactions. Nrf2-IN-3 sensitizes KEAP1-mutated cancer cells to Cisplatin (HY-17394) and Gefitinib (HY-50895) by repairing the mKEAP1/NRF2 complex[1].
Nrf2 activator-1 is a potent activator of NF-E2 related factor 2 (Nrf2). Nrf2 activator-1 has the potential for the treatment of COPD and other respiratory diseases, including asthma, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis (extracted from patent WO2018109647A1)[1].
S-allylmercaptocysteine, an organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. S-allylmercaptocysteine achieves its anti-cancer effect through a variety of pathways such as inducing the apoptosis of cancer cells through the TGF-β signaling pathway, or reducing the NF-κB activity and up-regulating Nrf2 to achieve the effects of anti-inflammation and anti-oxidation[1][2][3].
Hinokitiol is a component of essential oils isolated from Chymacyparis obtusa, reduces Nrf2 expression, and decreases DNMT1 and UHRF1 mRNA and protein expression, with anti-infective, anti-oxidative, and anti-tumor activities.
Dimethyl fumarate-d2 is the deuterium labeled Dimethyl fumarate[1]. Dimethyl fumarate (DMF) is an orally active and brain-penetrant Nrf2 activator and induces upregulation of antioxidant gene expression. Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway, and also induces cell autophagy. Dimethyl fumarate can be used for multiple sclerosis research[2][3].
Ezetimibe ketone (EZM-K) is a phase-I metabolite of Ezetimibe. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator. Ezetimibe is a potent cholesterol absorption inhibitor[1][2][3].
Eriodictyol-7-O-glucoside (Eriodictyol 7-O-β-D-glucoside), a flavonoid, is a potent free radical scavenger. Eriodictyol-7-O-glucoside is also an Nrf2 activator, confers protection against Cisplatin-induced toxicity[1].
I-152 is a conjugate containing N-acetyl-cysteine (NAC) and cysteamine (MEA). I-152 activates NRF2 and ATF4 signals. I-152 has anti-proliferative properties[1].
Dimethyl fumarate D6 is a deuterium labeled Dimethyl fumarate. Dimethyl fumarate is a nuclear factor (erythroid-derived)-like 2 (Nrf2) pathway activator and induces upregulation of antioxidant gene expression[1][2][3][4][5][6].
Gingerenone A is a Nrf2-Gpx4 activator with anti-breast-cancer properties. Gingerenone A results a delayed G2/M in cancer cells, following oxidative stress and senescence responses. Gingerenone A also alleviates ferroptosis in secondary liver injury (SLI) in dextran sodium sulfate (DSS)-induced colitis mice. Gingerenone A can be isolated from Zingiber officinale[1][2].
Rosolic Acid is an activator of Nrf2, as well as its downstream targets. Rosolic Acid increases the levels of angiogenic factors, decreases inflammation (TNF-α and IL-1β) and apoptotic markers (CXCL10 and CCL2). Rosolic Acid restores the function of pancreatic cells and protects endothelial cells (ECs) from endoplasmic reticulum stressed[1].
Sarmentosin is an activator of Nrf2. Sarmentosin inhibits mTOR signaling and induces autophagy-dependent apoptosis in human HCC cells[1].
Pyridoxine hydrochloride (Pyridoxol; Vitamin B6) is a pyridine derivative. Pyridoxine (Pyridoxol; Vitamin B6) exerts antioxidant effects in cell model of Alzheimer's disease via the Nrf-2/HO-1 pathway.
Corynoline, isolated from Corydalis incise (Papaveraceae), is a reversible and noncompetitive acetylcholinesterase (AChE) inhibitor with an IC50 of 30.6 μM[1]. Corynoline exhibits anti-inflammatory activity by activating Nrf2[2].
Bardoxolone is a synthetic triterpenoid compound with potential antineoplastic and anti-inflammatory activities, acting as an activator of the Nrf2 pathway and an inhibitor of the NF-κB pathway.
Curcumin D6 (Diferuloylmethane D6) is a deuterium labeled Curcumin (Turmeric yellow). Curcumin (Turmeric yellow) is a natural phenolic compound with diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Curcumin is an inhibitor of p300 histone acetylatransferase (HATs) and also shows inhibitory effects on NF-κB and MAPKs.
NXPZ-2 is an orally active Keap1-Nrf2 protein–protein interaction (PPI) inhibitor with a Ki value of 95 nM, EC50 value of 120 and 170 nM. NXPZ-2 can dose-dependently ameliorate Aβ[1-42]-Induced cognitive dysfunction, improve brain tissue pathological changes in Alzheimer’s disease (AD) mouse by increasing neuron quantity and function. NXPZ-2 can inhibit oxidative stress by increasing Nrf2 expression levels and promoting its cytoplasm to nuclear translocation, which is helpful for Keap1-Nrf2 PPI inhibitors and AD associated disease research[1].
Artemisitene, a natural derivative of Artemisinin, is a Nrf2 activator with antioxidant and anticancer activities. Artemisitene activates Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability[1][2].
Sanggenon A (Sanggenone A) exerts anti-inflammatory effects by regulating NF-κB and HO-1/Nrf2 signaling pathways in BV2 and RAW264.7 cells. Sanggenon A markedly inhibits the Lipopolysaccharide (LPS; HY-D1056)-induced production of nitric oxide[1].
Ezetimibe (SCH 58235) is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator. Ezetimibe (SCH 58235) is a potent cholesterol absorption inhibitor.
Nrf2 activator-6, a tetrahydroisoquinoline compound, is a Nrf2 activator. Nrf2 activator-6 has an IC50 of 5 nM for inhibiting the Kelch domain-Nrf2 interaction (WO2021214470A1; Example 4)[1].
Methyllucidone is a neuroprotective agent and an antioxidant that can be isolated from Lindera erythrocarpa Makino. Methyllucidone inhibits the ROS production, and activates antioxidant signaling pathways that include Nrf-2 and PI3K[1].
seco-Isolariciresinol Diglucoside, a synthetic lignin, which is derived from the natural plant flaxseed. seco-Isolariciresinol Diglucoside reduces asbestos-induced NLRP3 expression, and NF-κB activation in macrophages (MF). seco-Isolariciresinol Diglucoside also activates Nrf2.
CDDO-dhTFEA (RTA dh404) is a synthetic oleanane triterpenoid compound which potently activates Nrf2 and inhibits the pro-inflammatory transcription factor NF-κB[1]. CDDO-dhTFEA restores hypertension (MAP), increases Nrf2 and expression of its target genes, attenuates activation of NF-κB and transforming growth factor-β pathways, and reduces glomerulosclerosis, interstitial fibrosis and inflammation in the chronic kidney disease (CKD) rats[2].
Ezetimibe-d4 is deuterium labeled Ezetimibe. Ezetimibe (SCH 58235) is a potent cholesterol absorption inhibitor. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator.
Brusatol, isolated from the Brucea javanica plant, inhibits Nrf2.
NRF2 inhibitor AEM1 is a specific small molecule inhibitor of Nrf2 transcriptional activity in cancer cells, shows no activity against a panel of >100 kinases (including isoforms of PI3K, AKT, and PKC); broadly decreases the expression of Nrf2 controlled genes (HMOX1, GPX2), sensitizes A549 cells to various chemotherapeutic agents, and inhibits the growth of A549 cells in vitro and in vivo.
An inducer of NRF2 that selectively activates NRF2 signaling with CD value (The concentration that doubles the specific activity) of 0.18 uM; covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein KEAP1, arrests KEAP/NRF2 complex in the closed conformation in live cells; potently represses the release of the proinflammatory cytokine IL-6 in primary mouse HD and WT microglia and astrocytes.