Keap1-Nrf2 Inhibitor

Pteryxin ((+)-Pteryxin) is an orally active multi-target inhibitor that targets NF-κB, MAPK, NLRP3 inflammasome, and Nrf2/ARE pathways. Pteryxin is also a BChE inhibitor (IC₅₀=12.96 μg/mL) with a low inhibitory efficiency on AChE. Pteryxin inhibits the Ca²⁺-calcineurin-NFATc1 pathway by blocking NF-κB/MAPK signaling, inhibiting NLRP3 inflammasome activation, and reducing ROS generation, and activates Nrf2-mediated antioxidant enzyme expression. Pteryxin has anti-inflammatory, antioxidant, and osteoclastogenesis inhibitory activities. Pteryxin can be used in the study of inflammatory diseases, osteoporosis, diabetes, and Alzheimer's disease.

Garcinone E is a xanthone natural product that exerts antioxidant, anti-inflammatory, antitumor, and immunomodulatory activities by inhibiting JNK, TNF-α, NF-κB, and FAS, and enhancing Nrf2 signaling pathways. Garcinone E can be used in research on autoimmune hepatitis, obesity, and various cancers (including breast cancer, colorectal cancer, cervical cancer, liver cancer, lung cancer, and gastric cancer).

Quinocetone is an orally active animal feed additive used to increase the meat production of livestock and poultry. Quinocetone exhibits antibacterial activity against a variety of pathogenic microorganisms. Quinocetone exhibits tissue-specific (liver, lymphocyte) toxicity. Quinocetone induces autophagy in cells through the ATF6/DAPK1 pathway. Quinocetone activates the NF-κB and iNOS pathways, leading to cell apoptosis, hepatocyte vacuolar degeneration and fibrosis. Quinocetone can inhibit Nrf2/HO-1 and induce the generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage.

biKEAP1 (compound 3) is an inhibitor targeting the dimerKEAP1. biKEAP1 binds to cellular KEAP1 dimers and releases the NRF2 protein sequestered by KEAP1, resulting in immediate activation of NRF2. biKEAP1 also promotes nuclear translocation of NRF2 and directly inhibits proinflammatory cytokine transcription. biKEAP1 can reduce acute inflammation and reduce inflammatory damage in acute inflammation models.

Phytol (Standard) is the analytical standard of Phytol. This product is intended for research and analytical applications. Phytol ((E)-Phytol) is an orally active diterpenoid alcohol that can be extracted from chlorophyll. Phytol has antioxidant, anti-inflammatory, anti-schistosomiasis and antibacterial activities[1][2][3].

Nrf2 activator-12 (compund 10v) potently activates Nrf2 (EC50=83.5 nM) and exhibits promising pharmacological properties, reversing disease progression and alleviating demyelination in an experimental autoimmune encephalomyelitis mouse model.

Nrf2-ARE/hMAO-B/QR2 modulator 1 is a Resveratrol-based multitarget-directed ligands with IC₅₀s of 8.05, 9.83 and 0.57 μM for hMAO-B, NRF2 and QR2. Nrf2-ARE/hMAO-B/QR2 modulator 1 has neuroprotection, decreasing ROS production in okadaic acid-treated mice hippocampal slices. Nrf2-ARE/hMAO-B/QR2 modulator 1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Nodosin is an orally active diterpenoid compound that can be isolated from Isodon serra. Nodosin can inhibit the proliferation and induce cell cycle arrest and apoptosis of tumor cells. Nodosin can also inhibit oxidative stress, inflammatory responses, and ferroptosis. Nodosin has anti-inflammatory and anti-tumor activities.

Keap1-Nrf2-IN-9 (Compound 11) is a potent Keap1-Nrf2 PPI (Keap1-Nrf2 protein-protein interaction) inhibitor with an IC₅₀ of 0.575 μM. Keap1-Nrf2-IN-9 increases 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. Keap1-Nrf2-IN-9 shows no cytotoxic activity in ARPE19 cells.

Keap1-Nrf2-IN-13 is a Keap1-Nrf2 protein–protein interaction (PPI) inhibitor with an IC₅₀ value of 0.15 μM. Keap1-Nrf2-IN-13 has strong binding affinities to the Keap1 protein by forming hydrogen bond with the key polar residues (Asn414, Arg415, Arg483, Gln530). Keap1-Nrf2-IN-13 can be used in the research of oxidative stress-related and inflammatory diseases, including pulmonary fibrosis, chronic obstructive pulmonary disorder (COPD) and cancers.

Toralactone, isolated from Cassia obtusifolia, mediates hepatoprotection via an Nrf2-dependent anti-oxidative mechanism.

5-(3',4'-Dihydroxyphenyl)-γ-valerolactone is an intestinal microbiota metabolite of (-)-Epicatechin (HY-N0001). 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone downregulates TNF-α-stimulated phosphorylation of IKK and IκBα, inhibits the transcriptional activation of NF-κB, and suppresses the expression of adhesion molecules and chemokines. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone promotes autophagy, alleviates oxidative stress, maintains osteoblast differentiation, induces G₁ phase arrest, inhibits adipogenesis, and scavenges ABTS free radicals. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone inhibits the adhesion of uropathogenic Escherichia coli to bladder epithelial cells; when used in combination with Curcumin (HY-N0005), it downregulates the NLRP3 and NOX2/Nrf2 signaling pathways, thereby reducing microglial activation. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone can be used in research related to diabetes, atherosclerosis, osteoporosis, obesity, neurodegenerative diseases involving microglial activation, and urinary tract infections.

Keap1-Nrf2-IN-7 (compound 7v) is a potent Keap1-Nrf2 PPI (Keap1-Nrf2 protein−protein interaction) inhibitor with an IC₅₀ of 0.45 µM.

Benzanthrone is an immunotoxic, pro-inflammatory Photosensitizer. Benzanthrone upregulates iNOS, COX-2 and inflammatory cytokines; activates ERK1/2, p38, JNK, AP-1 and NF-κB; inhibits Nrf2; and induces oxidative stress and DNA damage. Upon radiation exposure, Benzanthrone generates singlet oxygen and superoxide anion radicals, induces photohemolysis and lipid peroxidation, and alters the levels of skin xenobiotic enzymes. Benzanthrone exhibits differential genotoxicity in different cell lines. Benzanthrone possesses skin tumor-initiating and promoting activities. Benzanthrone can be used in skin tumor-related studies.

BPK-29 hydrochloride is a specific ligand that disrupts the atypical orphan nuclear receptor NR0B1-protein (such RBM45 and SNW1) interactions by covalently modifying C274. BPK-29 hydrochloride impairs the anchorage-independent growth of KEAP1-mutant cancer cells.

Aureusidin is a flavonoid compound that is isolated and extracted from Antirrhinum majus and exhibits oral activity. Aureusidin possesses antioxidant, neuroprotective, and anti-inflammatory properties. Aureusidin directly targets and binds MD2 and Caspase-3 with high affinity, synergistically inhibits the TLR4/NF-κB inflammatory pathway and GSDME-mediated pyroptosis, and activates the Nrf2/HO-1 antioxidant axis via the ROS/MAPKs pathway. Aureusidin is a bovine liver arginase inhibitor with an IC₅₀ of 57.1 µM. Aureusidin is used for research on inflammation-related diseases (osteoarthritis), acute liver injury, and endothelial dysfunction.

Nrf2-IN-4 is a Nrf2 inhibitor. Nrf2-IN-4 induces ferroptosis via NRF2 inhibition. Nrf2-IN-4 disrupts cellular iron homeostasis, facilitates ferritin degradation, and ultimately triggers ferroptosis. Nrf2-IN-4 induces lysosome activation by promoting iron-dependent ROS production and lysosomal acidification. Nrf2-IN-4 demonstrates significant antitumor efficacy. Nrf2-IN-4 can be used for the study of breast cancer.

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.

Brusatol (Standard) is the analytical standard of Brusatol (HY-19543). This product is intended for research and analytical applications. Brusatol (NSC 172924) is a unique inhibitor of the Nrf2 pathway that sensitizes a broad spectrum of cancer cells to Cisplatin and other chemotherapeutic agents. Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism. Brusatol can be developed into an adjuvant chemotherapeutic agent. Brusatol increases cellular apoptosis.

Keap1-Nrf2-IN-23 (compound 56) is an inhibitor of the Keap1–Nrf2 PPI (IC₅₀=16.0 nM). Keap1-Nrf2-IN-23 binds to Keap1 with a K_d value of 3.07 nM. Keap1-Nrf2-IN-23 has oral activity.