Keap1-Nrf2-IN-10 (compound 15) is a potent inducer of NQO1 and efficaciously mitigates oxidative stress in gamma-irradiated mice by reducing MDA and ROS levels, as well as NQO1 in the liver, which enhances the survival rate of these mice [1].

Keap1-Nrf2-IN-9 (compound 11) is a potent inhibitor of the Keap1-Nrf2 protein−protein interaction (PPI) with an IC50 value of 0.575 µM. It enhances the expression of Nrf2 target genes, including heme oxygenase 1 (Hmox1), glutathione S-transferase P (GstP), and glutamate-cysteine ligase catalytic (Gclc) and modulatory (Gclm) subunits. Notably, Keap1-Nrf2-IN-9 is not cytotoxic to ARPE19 cells [1].

Keap1-Nrf2-IN-14 is a KEAP1-NRF2 inhibitor that effectively disrupts the KEAP1-NRF2 interaction (IC50: 75 nM) with a Kd=24 nM for KEAP1. Keap1-Nrf2-IN-14 induces the expression of NRF2 target genes and is able to enhance downstream antioxidant and anti-inflammatory effects. -Nrf2-IN-14 can be used to study oxidative stress-related inflammation.

Keap1-Nrf2-IN-15 (Compound 24a) is a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, displaying IC50 values of 77 nM in a fluorescence polarization (FP) assay and 2.5 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay [1].

Keap1-Nrf2-IN-16 is a biologically active peptide with KEAP1 binding activity.

Keap1-Nrf2-IN-1 TFA (compound35) is a Keap1-Nrf2 protein-protein interaction inhibitor (IC50: 43 nM) that activates Nrf2-regulated cytoprotective responses. Keap1-Nrf2-IN-1 TFA antagonizes acetaminophen-induced liver injury in cellular and in vivo models.

Keap1-Nrf2-IN-5 is a potent inhibitor of Keap1-Nrf2 PPI (Keap1-Nrf2 protein-protein interaction) (IC50: 4.1 μM, Kd: 3.7 μM).

Keap1-Nrf2-IN-13 is a potent inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI), exhibiting an IC50 value of 0.15 μM, indicative of its high efficacy. It binds strongly to the Keap1 protein by forming hydrogen bonds with critical polar residues (Asn414, Arg415, Arg483, Gln530), showcasing its specificity. This compound has implications for research into diseases associated with oxidative stress and inflammation, such as pulmonary fibrosis, chronic obstructive pulmonary disorder (COPD), and cancers, due to its mechanism of action.

Keap1–Nrf2 IN-1 activates Nrf2-regulated cytoprotective response and antagonizes acetaminophen-induced liver injury both in cellular and in vivo models. Keap1–Nrf2 IN-1 is a Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (

Keap1-Nrf2-IN-6 is a potent, selective inhibitor of the Keap1-Nrf2 protein−protein interaction (PPI), demonstrating an inhibitory concentration (IC50) of 41 nM and a dissociation constant (Kd) of 68 nM.

Keap1-Nrf2-IN-11 (Compound 6k), a potent Keap1-Nrf2 inhibitor, exhibits a dissociation constant (KD) of 0.21 nM. It hampers the production of reactive oxygen species (ROS) and nitric oxide (NO), as well as the expression of tumor necrosis factor-alpha (TNF-α). By promoting Nrf2 nuclear translocation, it mitigates inflammation and is utilized in anti-inflammatory studies [1].

Keap1-Nrf2-IN-4, a powerful neddylation inhibitor, demonstrates significant anti-proliferation activity against MGC-803 cells (IC50 = 2.55 μM), effectively impeding their migration and inducing apoptosis. Additionally, it effectively inhibits tumor growth while exhibiting minimal toxicity [1].

eap1-Nrf2-IN-12 is a potent inhibitor of Keap1-Nrf2 (IC50: 2.30 μM). eap1-Nrf2-IN-12 is metabolically stable in human liver microsomes.

Keap1-Nrf2-IN-3 is a KEAP1:NRF2 protein protein interaction inhibitor, and with a K d value of 2.5 nM for KEAP1 protein.

Omaveloxolone (RTA-408) (RTA-408) is a synthetic triterpenoid that activates the cytoprotective transcription factor Nrf2 and inhibits NF-κB signaling. Phase 2.

Curcumin (Natural Yellow 3) is a phenolic natural product, an inhibitor of histone acetyltransferase p300/CREB (IC50=25 μM) with specificity. Curcumin has a wide range of pharmacological activities such as antitumor, anti-inflammatory and antioxidant.

ML385 is an NRF2 inhibitor (IC50=1.9 μM) with novelty and specificity. ML385 has anti-inflammatory activity by modulating anti-oxidative stress through the inhibition of NRF2. ML385 also exhibits anti-tumor activity.

1. Farrerol has antioxidative activity.2. Farrerol modulates TAP and BNBD5 gene expression in mammary gland, enhances bMEC defense against S. aureus infection and could be useful in protection against bovine mastitis. 3. Farrerol inactivates KEAP-1 or act

TAT 14 acetate, a 14-mer peptide, is an Nrf2 activator with anti-inflammatory properties. TAT 14 acetate increases Nrf2 protein levels due to targeting the Nrf2 binding site on Keap1, but has no effect on Nrf2 mRNA expression.

Nrf2-IN-1 is an nuclear factor-erythroid 2-related factor 2 (Nrf2) inhibitor. Nrf2-IN-1 is developed for the research of acute myeloid leukemia (AML).

Ezetimibe (SCH 58235) is a Dietary Cholesterol Absorption Inhibitor. The physiologic effect of ezetimibe is by means of Decreased Cholesterol Absorption.

Resveratrol (SRT 501) is a polyphenolic natural product, a plant antitoxin with antioxidant and chemopreventive activities. Resveratrol has a wide range of targets including COX, SIRT, LOC, etc. Resveratrol induces autophagy and apoptosis.

4-hydroxyphenylacetic acid (parahydroxy phenylacetate) is a major microbiota-derived metabolite of polyphenols. 4-hydroxyphenylacetic acid(p-Hydroxyphenylacetic acid) is involved in the antioxidative action. 4-hydroxyphenylacetic acid(p-Hydroxyphenylacetic acid) induces expression of Nrf2.

Danshensu (Dan shen suan A) is an active ingredient of Salvia miltiorrhiza with wide cardiovascular benefit.

Bardoxolone Methyl (TP-155) is a synthetic triterpenoid that acts as an activator of the Nrf2 pathway and an inhibitor of the NF-κB pathway with potential anti-tumor and anti-inflammatory activities.

Luteolin (Luteolol) belongs to the flavonoid group of natural products and is a Nrf2 inhibitor, PDE inhibitor. Luteolin has a wide range of biological activities including antitumor, antioxidant, anti-inflammatory, antimicrobial, antiviral, antiallergic, and procoagulant.

AKOS B018304 is an aryl derivative capable of polarity substitution at the para position.AKOS B018304 is a chikungunya virus inhibitor.

1. Eriodictyol (Huazhongilexone) is a flavonoid with anti-inflammatory and antioxidant activities. 2. Eriodictyol may possess antidiabetic properties through increasing glucose uptake and improving insulin resistance. 3. Eriodictyol may be a potential therapeutic resource for Atopic dermatitis and an adjunctive agent to control itchiness inAtopic dermatitis.

Nrf2 activator; inhibits Nrf2/Keap1 interaction. Induces upregulation of Nrf2 pathway downstream gene expression including heme-oxygenase 1. Suppresses LPS-induced TNF-α expression in THP-1 cells.

Nrf2 activation of the antioxidant response element (ARE) is central to cytoprotective gene expression against oxidative and/or electrophilic stress. Unless activated by inflammatory, environmental, or oxidative stressors, Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. Because of its protective capabilities, small molecules that activate Nrf2 signaling are being examined as potential anti-cancer or anti-inflammatory agents. DL-Sulforaphane N-acetyl-L-cysteine (SFN-NAC) is a major metabolite of SFN , a powerful inducer of chemopreventative enzymes via Keap1-Nrf2 signaling and ARE-driven gene expression. At 75 μM, SFN-NAC has been shown to increase ARE expression in HepG2-C8 cells. Its reported potency on ARE-related gene expression is roughly 8-fold less than SFN.

Dehydroglyasperin C is a potent NAD(P)H:oxidoquinone reductase (NQO1) and phase 2 enzyme inducer. Dehydroglyasperin C possesses potent antioxidant, cancer chemopreventive, and neuroprotective activities, it has protective effects against chronic diseases

Pelargonidin chloride shows protective effect against CTN-induced oxidative stress in HepG2 cells and up-regulated the activity of detoxification enzyme levels through Keap1/Nrf2 signaling pathway.

(R)-5-Hydroxy-1,7-diphenylheptan-3-one ((5R)-Dihydroyashabushiketol) is extracted from the rhizomes of Alpinia officinarum, a Chinese medicinal herb. (R)-5-Hydroxy-1,7-diphenylheptan-3-one inhibits melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells.

Pyridoxine (Vitamin B6) is the 4-methanol form of vitamin B6 and is converted to pyridoxal 5-phosphate in the body. Although pyridoxine and vitamin B6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading.

Nrf2/Keap1 and Keap1/Cul3 interaction inhibitor

MIND4-17, a potent NRF2 activator, covalently modifies the C151 residue of Keap1, disrupting the Keap1-Nrf2 association. This action leads to the stabilization and nuclear translocation of the Nrf2 protein, consequently exerting potent antioxidant activity.

Dimethyl fumarate (DMF), a fumarate derivative, is used as antiinflammatory and immunomodulatory agent.

CBR-470-1 is a potent inhibitor of glycolytic phosphoglycerate kinase 1 (PGK1) that activates NRF2 by increasing methylglyoxal levels. CBR-470-1 is a non-covalent Nrf2 activator with neuroprotective activity that protects SH-SY5Y neuronal cells from MPP+-induced cytotoxicity by activating the Keap1-Nrf2 cascade. cytotoxicity induced by MPP+.

4-Octyl Itaconate is a cell-permeable derivative of Itaconate, an anti-inflammatory metabolite. 4-Octyl Itaconate activates Nrf2 via alkylation of KEAP1 and also inhibits phosphorylation of STING. 4-Octyl Itaconate is an anti-inflammatory metabolite.

Kinsenoside ((+)-Kinsenoside) shows significant antihepatotoxic, and anti-inflammatory activities. Kinsenoside could be useful for repairing beta cells in pancreatic islet injury as well as improving its function, it could promote the glucose tolerance of acute glucose increase in both diabetic and normal healthy rats. Kinsenoside inhibits osteoclastogenesis from macrophages by attenuating RANKL-induced NF-κB and NFATc1 activities, which in turn, prevents bone loss from OVX mice.

CDDO-dhTFEA, a synthetic oleanane triterpenoid, effectively activates Nrf2 while inhibiting the NF-κB pro-inflammatory transcription factor. It restores mean arterial pressure (MAP), elevates Nrf2 levels and the expression of related genes, attenuates NF-κB and transforming growth factor-β pathway activation, and mitigates glomerulosclerosis, interstitial fibrosis, and inflammation in rats with chronic kidney disease (CKD).

NK-252 is a potential activator of Nrf2. It has great Nrf2-activating potential.

2-tert-Butyl-1,4-benzoquinone (TBQ), an electrophilic metabolite of butylated hydroxyanisole (BHA), causes activation of Nrf2 together with S-arylation of its negative regulator Keap1 in RAW264.7 cells.

S217879 is a potent and selective activator of NRF2 that disrupts the KEAP1-NRF2 interaction, resulting in significant activation of the NRF2 pathway. This compound is applicable in research on non-alcoholic steatohepatitis (NASH) [1].

Praelolide, a potent Nrf2 activator, disrupts Keap1-Nrf2 protein-protein interactions through noncovalent binding to Keap1, inhibiting osteoclastogenesis and the production of reactive oxygen species (ROS). With its potential in osteoclastogenic bone disease research, Praelolide presents a promising avenue for therapeutic exploration.

Oltipraz (RP 35972) is a synthetic dithiolethione with potential chemopreventive and anti-angiogenic properties. Oltipraz induces phase II detoxification enzymes, such as glutathione S transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). The induction of detoxification enzymes enhances the detoxification of certain cancer-causing agents, thereby enhancing their elimination and preventing carcinogen-induced DNA damages. Although the exact mechanism through which the anti-angiogenesis effect remains to be fully elucidated, oltipraz maybe able to modulate the expression of a number of angiogenic factors, thereby blocking the sustained and focal neovascularization in multiple tumor cell types.

Brusatol (NSC-172924) is a natural product isolated from the Brucea javanica plant. It inhibits Nrf2.

Bardoxolone (CDDO) is a synthetic oleanane triterpenoid that blocks the cellular synthesis of inducible nitric oxide synthase and inducible COX-2 in INF-γ-activated mouse macrophages with an IC50 value of 0.4 nM. By suppressing reactive oxygen and nitrogen species (ROS/RNS) formation, it promotes the cellular control of ROS/RNS levels that would lead to DNA damage associated with tumorigenesis. In various Y cell lines, Bardoxolone has been shown to specifically inhibit proliferation and induce apoptosis. Mechanism studies revealed that Bardoxolone is a ligand for peroxisome proliferator-activated receptor γ, and also that it induces genes regulated by Nrf2, including heme oxygenase-1 and eotaxin-1, which play a role in antioxidant response element signaling activity.

Toralactone is a natural product isolated from Cassia obtusifolia, mediates hepatoprotection via an Nrf2-dependent anti-oxidative mechanism

1. Corynoline ((+)-Corynoline) is an acetylcholinesterase inhibitor.