Nrf2

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.

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

VVD-130037 is a small molecule activator specifically targeting Kelch-like ECH-associated protein 1 (KEAP1) with potential antitumor activity.VVD-130037 inhibits tumor growth in advanced solid tumors by degrading NRF2.

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

Sulforaphane is a natural isothiocyanate that activates Nrf2 and inhibits AMPK-dependent signaling. Sulforaphane has antitumor and anti-inflammatory activities by increasing the transcription of tumor suppressor proteins and inhibiting histone deacetylase activity.

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

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.

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.

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.

Antroquinonol is a ubiquinone derivative from Antrodia camphorata with anti-inflammatory and anticancer activities.Antroquinonol reduces oxidative stress and inhibits inflammation and sclerosis in mice with focal segmental glomerulosclerosis through enhancement of the Nrf2 signaling pathway.Antroquinonol has potential for use in the treatment of non-small cell lung cancer. Antroquinonol has potential for the treatment of non-small cell lung cancer and may be used in colon cancer research.

Nrf2 degrader 30 is a small molecule PROTAC that inhibits the degradation of Nrf2, thereby enhancing its activity. Nrf2 is a key transcription factor that regulates cellular antioxidant responses and various protective mechanisms. The activity of Nrf2 is primarily regulated by its interaction with Keap1, which serves as an E3 ubiquitin ligase complex adapter to promote Nrf2 ubiquitination and proteasomal degradation。

Gingerenone A is an effective Nrf2-Gpx4 activator. It is a small molecule compound isolated from ginger. It has anti-cancer activity, can prolong the cell cycle of cancer cells, and can inhibit dextran sodium sulfate (DSS)-induced colitis. Ferroptosis in secondary liver injury (SLI) in mice.

Tricetin is a flavonoid isolated from pomegranate.Tricetin is a potent competitive inhibitor of Keap1-Nrf2 protein-protein interaction (PPI) and protects Parkinson's disease patients from 6-OHDA-induced neurotoxicity by activating the Nrf2 HO-1 signaling pathway and blocking mitochondria-dependent apoptotic pathways.Tricetin Inhibits migration and expression of the indicator protease progerin-1 (PS-1) in nasopharyngeal carcinoma through the Akt GSK-1β pathway.Tricetin inhibits endothelial inflammation induced by oxidized LDL mediated by Egr-1, and protects rat chondrocytes from IL-1β-induced inflammation and apoptosis.Tricetin is an inhibitor of endothelial inflammation induced by oxidized LDL mediated by Egr-1 and protects against IL-1β-induced inflammation and apoptosis.

Rosolutamide (ALZ-003) is a curcumin analog, an orally active Nrf1 and Nrf2 activator.Rosolutamide modulates oxidative homeostasis, improves mitochondrial function and promotes autophagy, reduces mutant protein aggregation, and decreases intracellular mitochondrial reactive oxygen species (ROS) levels.Rosolutamide has been used in the study of neurodegeneration such as spinal cerebellar ataxia and Huntington disease. neurodegenerative diseases such as Huntington's disease. Regulates oxidative homeostasis.

Nrf2-ARE hMAO-B QR2 modulator 1, a resveratrol derivative and multi-target-directed ligand (mtdl), activated the NRF2-ARE pathway (CD = 9.83 μM), selectively inhibited hMAO-B and QR2（quinone reductase-2，NQO2) (IC 50 = 8.05 and 0.57 μM), and was able to promote hippocampal neurogenesis and exert neuroprotective and antioxidant effects in an Alzheimer's disease model.

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.

Carnosol is an Nrf2 activator, increasing Nrf2 levels and promoting heme oxygenase 1 (HMOX1) expression. It is a ribosomal S6 kinase (RSK2) inhibitor and can be used in gastric cancer-related research with an IC50 value of approximately 5.5 μM.

CDDO-EA (CDDO ethyl amide) is an activator of the Nrf2 antioxidant response element.

Sappanone A is a high isoflavanone that exhibits anti-inflammatory effects by modulating Nrf2.Sappanone A attenuates allergic airway inflammation in ovalbumin-induced asthma.

Danshensu (Dan shen suan A) is an active ingredient of *Salvia miltiorrhiza* with extensive cardiovascular benefits.

Nrf2 activator-1 is a potent activator of NF-E2-related factor 2 (Nrf2) and can be used to study COPD and other respiratory diseases, including asthma, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and pulmonary fibrosis.

Hydrangenol is a natural product and can be isolated from Hydrangea serrata leaves. Hydrangenol is an antiphotoaging compound with oral activity. Hydrangenol can reduce MMP and inflammatory cytokine expression and increase moisturizing factors and antioxidant genes level, result in preventing wrinkle formation.

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.

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.

Ezetimibe (SCH 58235) is a dietary cholesterol absorption inhibitor that exerts its physiologic effect by decreasing cholesterol absorption.

KI696 is a high-affinity probe that potently inhibits the interaction of Keap1 and NRF2.

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.

Pyridoxine hydrochloride (Vitamin B6) is the 4-methanol form of vitaminB6 which is converted to pyridoxal phosphate which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid.

Dimethyl fumarate (DMF) is an Nrf2 activator with oral activity and blood-brain barrier permeability. Dimethyl fumarate has antimicrobial, anti-inflammatory, and immunomodulatory activities and has been used in the study of multiple sclerosis.

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.

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.

TBHQ (tert-Butylhydroquinone) is an antioxidant that induces an antioxidant response through the redox-sensitive transcription factor Nrf2.

Nrf2-IN-3 is a mKEAP1-selective NRF2 inhibitor that selectively binds KEAP1 mutants and restores their NRF2 inhibitory function by repairing the disrupted KEAP1 NRF2 interaction, and selectively sensitizes cisplatin in xenografts of mouse mKEAP1 cancer cells.

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.

3',4',5',5,7-Pentamethoxyflavone is a naturally occurring brassinosteroid compound from the Rutaceae family that exhibits cancer cell resistance by inhibiting the Nrf2 pathway to overcome chemotherapeutically active molecules.

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).

Eriodictyol-7-O-glucoside is an Nrf2 activator conferring protection against Cisplatin-induced toxicity. Eriodictyol-7-O-glucoside is a flavonoid and a free radical scavenger with antioxidant activity in pistachio skin.

Moringin is an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucoMoringin present in Moringa oleifera seeds. Moringin has anti-inflammatory and antioxidative properties.

Hinokitiol (4-Isopropyltropolone) can inhibit ultraviolet B-induced apoptosis in keratinocytes and strongly suggest that the inhibitory mechanism is due to the antioxidant activity of metallothionein induced by the agent. Also, Hinokitiol modulates estrogen receptor signaling and inhibits proliferation of human breast cancer cells.

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

Mangiferin (Hedysarid) is used for antidiabetes. Extracted from Mangifera indica L.

(-)-Perillaldehyde shows antibacterial activity.

1,7-Diphenyl-4-hepten-3-one is a compound isolated from Alpinia officinarum, which activates the Nrf2 pathway to suppress pyroptosis. It alleviates cognitive impairment and pathological damage in APP PS1 mice and prevents oxidative stress damage while reducing levels of pyroptosis-related proteins. 1,7-Diphenyl-4-hepten-3-one enhances Aβ-induced proliferation in HT22 cells and can be used in Alzheimer’s disease research.

(S)-(-)-Anatabine ((-)-Anatabine), an alkaloid present in tobacco, is an NRF2 activator that attenuates ovalbumin-induced asthma through oxidative stress and inflammation mitigation as well as up-regulation of Nrf2 HO-1 signaling in rats, and may be used in the study of autoimmune thyroiditis.

AEM1 is an inhibitor of deregulated NRF2 transcriptional activity in cancer. AEM1 acts by broadly decreasing the expression of NRF2 controlled genes, sensitizing A549 cells to various chemotherapeutic agents, and inhibiting the growth of A549 cells in vitro and in vivo.

Physalin B is one of the major active compounds from the Solanaceae family of plants and has a wide range of biological activities for the treatment of inflammatory eczema and herpes, among other diseases.Physalin B ameliorates lipopolysaccharide-induced inflammatory response due to acute lung injury by inhibiting NF-κB and NLRP3 through activation of the PI3K Akt pathway.Physalin B inhibits PDGF-BB-induced VSMC proliferation and migration and phenotypic transformation through activation of the Nrf2 pathway. Physalin B inhibits PDGF-BB-induced VSMC proliferation, migration and phenotypic transformation through activation of the Nrf2 pathway.Physalin B exerts antitumor activity by inhibiting LAP2α-HDAC1-mediated deacetylation of glioma-associated oncogene 1 and hepatic stellate cell activation.

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.

Astilbin (Neoastilbin) is actions Flavonoid phytochemical found in St. John′s wort and Traditional Chinese Medicine herbal preparations.