Keap1-Nrf2 Activator

Vitisin A ((+)-Vitisin A) is an orally active natural product with multiple pharmacological activities including anti-inflammatory, anti-tumor, anti-oxidant, anti-pathogenic microorganism, hypoglycemic and lipid-regulating, anti-osteoporotic, neuroprotective and cardiovascular protective effects. Vitisin A exhibits inhibitory effects on human AChE and MAO-B with IC₅₀ values of 1.29 µM and 4.94 µM, respectively. Vitisin A inhibits the ERK, MAPK, NF-κB, STAT1, HMGCR and TRAF6 pathways, downregulates the related phosphorylation and protein expression, while activates the Nrf2/HO-1 pathway and upregulates p21 expression. Vitisin A induces tumor cell apoptosis and cell cycle arrest, inhibits adipogenesis and lipid accumulation, while alleviates oxidative stress, suppresses inflammatory responses, blocks hepatic fibrosis, Cuproptosis and cholesterol synthesis, and increases the expression levels of central BDNF and TrkB. Vitisin A can be used in the research of tumors, infectious diseases, metabolic diseases, bone and joint diseases, liver diseases, skin injuries, as well as neurodegenerative and cognitive dysfunction-related diseases.

Desfluoro-ezetimibe is a desfluoro impurity of Ezetimibe. Ezetimibe is a potent, metabolically stable cholesterol absorption inhibitor. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator.

(+)-DHMEQ is an activator of antioxidant transcription factor Nrf2. (+)-DHMEQ is the enantiomer of (-)-DHMEQ. (-)-DHMEQ inhibits NF-kB than its enantiomer (+)-DHMEQ.

Pentagalloylglucose (Standard) is the analytical standard of Pentagalloylglucose. This product is intended for research and analytical applications. Pentagalloylglucose (Penta-O-galloyl-β-D-glucose) is an orally active gallic tannin compound and an inducer of apoptosis and autophagy. Pentagalloglucose induces cell apoptosis and autophagy through the GSK3β/β-catenin pathway. Pentagalloylglucose inhibits UBE2T-mediated p53 ubiquitination, upregulates p53, downregulates RRM1/RRM2 in pancreatic cancer organoids. Pentagalloglucose has antioxidant, anti mutagenic, anti-inflammatory, anticonvulsant, cardioprotective, anti allergic, cholesterol lowering, and anti-tumor activities.

Nrf2 activator-1 is an Nrf2 activator that acts on the Keap1-Nrf2 pathway. Nrf2 activation enhances antioxidant response-related transcription and promotes downstream cytoprotective responses such as NQO1. Nrf2 activator-1 is used in research on Nrf2 signaling and oxidative stress.

MIND4-17 is a potent NRF2 activator that covalently modifies a C151 residue of Keap1. MIND4-17 disrupts Keap1-Nrf2 association, leading to Nrf2 protein stabilization and nuclear translocation. MIND4‐17 exerts potent antioxidant activity.

12-Oxo phytodienoic acid (≥90%) (12-OPDA (≥90%)) is a plant lipid-derived anti-inflammatory compound. 12-Oxo phytodienoic acid (≥90%) induces the expression of SOCS-1 and inhibits LPS (HY-D1056)-induced activation of the NF-κB and p38 MAPK signaling pathways. 12-Oxo phytodienoic acid (≥90%) inhibits LPS-induced expression of IL-6 and TNF-α, and reduces LPS-induced NO production by decreasing iNOS levels. 12-Oxo phytodienoic acid (≥90%) induces activation of the Nrf2 signaling cascade. 12-Oxo phytodienoic acid (≥90%) can be used for the research of neurodegenerative diseases.

trans-Isoferulic acid (trans-3-Hydroxy-4-methoxycinnamic acid) is an aromatic acid that exhibits anti-inflammatory activity. trans-Isoferulic acid dephosphorylates PI3K/Akt, suppresses LPS (HY-D1056)-induced NF-κB activation, enhances Nrf2 activity, downregulates iNOS and COX-2 expression, induces HO-1 expression, inhibits NO and PGE₂ production, and scavenges hydroperoxyl radical. trans-Isoferulic acid can be used for research of inflammatiory diseases.

Pinobanksin is an antioxidant and anti-ferroptosis agent found in sunflower honey and propolis, with oral activity. Pinobanksin enhances Nrf2-mediated antioxidant defense, inhibits NF-κB inflammation, and suppresses apoptosis and ferroptosis in in vivo models and normal cells. Pinobanksin exhibits apoptosis-inducing effects on B-cell lymphoma cells. Pinobanksin can be used in research related to perfluorooctane sulfonate-induced renal/cardiac toxicity, acute colitis, and B-cell lymphoma.

(9S,13R)-12-Oxo phytodienoic acid ((9S,13R)-12-OPDA) is a mPGES-1 inhibitor and Nrf2 activator. (9S,13R)-12-Oxo phytodienoic acid selectively inhibits mPGES-1 expression and reduces inducible PGE₂ production without affecting COX-1 or COX-2. (9S,13R)-12-Oxo phytodienoic acid inhibits the phosphorylation of IKKβ, IκBα, and NF-κB (p65), blocks the nuclear translocation of p65, increases the nuclear translocation of Nrf2, and upregulates HO-1 expression. (9S,13R)-12-Oxo phytodienoic acid inhibits the differentiation of M0 macrophages toward the M1 phenotype and promotes differentiation toward the M2 phenotype. (9S,13R)-12-Oxo phytodienoic acid decreases the levels of NO, PGE₂, IL-1β, IL-6, iNOS, and PGD₂. (9S,13R)-12-Oxo phytodienoic acid can be used for inflammation research.

TML-6, an orally active curcumin derivative, inhibits the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ). TML-6 can upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-oxidative Nrf2 gene. TML-6 has the potential for Alzheimer’s disease (AD) research.

Necrosulfonamide-d₄ is the deuterium labeled Necrosulfonamide (HY-100573). Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.

Acetyl zingerone is an analog of Zingerone (HY-14621). Acetyl zingerone downregulates the expression of ROS metabolism-related genes, fibroblast senescence-related genes, keratinocyte differentiation-related genes, and IL-17A target genes. Acetyl zingerone inhibits the activities of MMP-1, MMP-3, and MMP-12, as well as the activation of NLRP3 inflammasome, pyroptosis (pyroptosis), ferroptosis (ferroptosis), cartilage destruction, and UVA-induced cyclobutane pyrimidine dimer formation. Acetyl zingerone upregulates the expression of collagen, proteoglycan, extracellular matrix glycoprotein, Notch pathway, and GPX4 gene, activates Nrf2 and HO-1, induces extracellular matrix synthesis and PINK1/Parkin-mediated mitophagy (mitophagy), and promotes chondrocyte survival. Acetyl zingerone alleviates the progression of osteoarthritis in mice. Acetyl zingerone can be used in research related to skin aging, inflammatory skin diseases, osteoarthritis, melanoma, and non-melanoma skin cancer.

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).

Tanshindiol C is a S-adenosylmethionine-competitive EZH2 (Histone Methyltransferase) inhibitor with an IC₅₀ of 0.55 μM for inhibiting the methyltransferase activity. Tanshindiol C is also an activator of both Nrf2 and Sirtuin 1 (Sirt1) in macrophages. Tanshindiol C possesses anti-cancer activity, and can be used for atherosclerosis research.

Selenomethionine (Standard) is the analytical standard of Selenomethionine. This product is intended for research and analytical applications. Selenomethionine is a naturally occurring amino acid containing selenium that has oral activity and is a common natural food source. Selenomethionine has antitumor activity[1][2][3].

Sarmentosin is an activator of Nrf2. Sarmentosin inhibits mTOR signaling and induces autophagy-dependent apoptosis in human HCC cells.

Tomentosin is an orally active natural sesquiterpenoid lactone. Tomentosin exhibits multiple activities such as anti-tumor, anti-fungal, anti-inflammatory, anti-oxidant and neuroprotective effects. Tomentosin can inhibit tumor cell proliferation, migration and invasion, and induce apoptosis. Tomentosin can be used in the research of tumors, inflammation and nervous system diseases.

Nrf2 activator-10 (Compound AI-1) is a PI3K-dependent inducer for antioxidant response element (ARE) (EC₅₀ is 2.7 μM) and an activator for Nrf2. Nrf2 activator-10 modifies Keap1, blocks Cul3-Keap1 ubiquitin ligase complex, activates the transcription of Nrf2. Nrf2 activator-10 protects cells from H₂O₂-induced apoptosis.

Nrf2-Activator-12G (compd 12g) is an activator of Nrf2. Nrf2-Activator-12G induces the expression of nrf2-dependentantioxidant enzymes at both mRNA and protein levels in DAergic neuronal cell. Nrf2-Activator-12G can used in study Parkinson’s Disease.