Quinone Reductase Activator

KI696 is a selective KEAP1/NRF2 protein-protein interaction inhibitor with a human K_d value of 1.3 nM. KI696 acts by competitively occupying the NRF2-binding pocket of the KEAP1 Kelch domain. KI696 blocks KEAP1-mediated ubiquitination and degradation of NRF2, promotes the translocation of NRF2 to the nucleus, activates the expression of downstream antioxidant genes, increases intracellular glutathione levels, and alleviates oxidative stress-induced cell damage and inflammatory cell infiltration in the lungs. KI696 reduces ozone-induced pulmonary oxidative damage and inflammatory cell accumulation in rats, and upregulates pulmonary antioxidant genes. KI696 can be used in research related to chronic obstructive pulmonary disease, oxidative stress and inflammation.

ML334 is a potent, cell permeable activator of NRF2 by inhibition of Keap1-NRF2 protein-protein interaction. ML334 binds to Keap1 Kelch domain with a K_d of 1 μM. ML334 stimulates NRF2 expression and nuclear translocation and induces antioxidant response elements (ARE) activity.

NK-252 is a potential Nrf2 activator, which exhibits a great Nrf2-activating potential.

4-Hydroxyphenyl acetate (4-HPA) is a natural antioxidant and protects cells from oxidative stress-induced necrosis. 4-Hydroxyphenyl acetate blocks the increase of cellular ROS induced by oxidative stress, and up-regulates NQO1 and HO-1 genes by stabilizing and inducing the nuclear translocation of NRF2 transcription factor.

Pelargonidin chloride is an anthocyanidin and also is a scavenger of nitric oxide radical and has antioxidant activities. Pelargonidin inhibits cell viability and induces cell cycle arrest at sub-G1 phase. Pelargonidin chloride increases the mRNA and protein expression of HO-1, NQO1, Nrf2. Pelargonidin chloride improves Aβ-induced memory and learning impairment.

Furaneol is mainly isolated from American grape (Vitis labrusca) and its hybrid grape. Furaneol is an important aroma compound in fruits and contribute to the strawberry-like note in some wines.

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).

Nrf2 activator-7 (Compound 12b) is a potent Nrf2 activator and significantly activates the Nrf2 signaling pathway.

FXR agonist 18 is an orally active FXR agonist, with an EC₅₀ of 10 nM against human FXR and an EC₅₀ of 1360 nM against human TGR5. FXR agonist 18 inhibits inflammatory responses by reducing nitrite production, downregulating the expression of pro-inflammatory genes (Tnf, Adgre1, Cyp8b1, upregulating the expression of FXR, Hmox1, Nqo1, Nrf2, and enhancing antioxidant responses. FXR agonist 18 ameliorates liver fibrosis in mice, exhibits protective effects in mice with cholestatic liver injury, and shows anti-MASH efficacy. FXR agonist 18 can be used in studies of metabolic dysfunction-associated steatohepatitis.

Antiproliferative agent-62 (compound 5) is a functionalized benzylidene-indolin-2-one with notable antiproliferative activity and NQO1 activity induciton funciton, particularly in inducing NQO1 expression in murine Hepa1c1c7 cells and demonstrating effectiveness against human cancer cell lines, including MCF-7 and HCT116.

AI-3 is a potent ARE (antioxidant response element) activator. AI-3 increases the NQO1 at the transcript levels and protein expression levels. AI-3 has the potential for the research of oxidative stress related diseases.

Tanshindiol B, a naphthaquinone diterpene, inhibits glioblastoma (GBM) growth by induction of noptosis (NQO1-dependent necrosis).

Keap1/Nrf2/ARE activator 2 is an activator of Keap1/Nrf2/ARE pathway and non-competitively inhibits AChE with an IC₅₀ of 14.79 μM and a K_i of 1.35 μM. Keap1/Nrf2/ARE activator 2 promotes Nrf2 nuclear translocation, leading to antioxidant gene upregulation and enhanced cellular defense against oxidative stress. Keap1/Nrf2/ARE activator exhibits robust neuroprotection against both H₂O₂- and Scopolamine (SCA) (HY-N0296)-induced injury in PC12 cells. Keap1/Nrf2/ARE activator 2 ameliorates memory impairment and the neuro-inflammation associated with SCA-initiated cognitive dysfunction in a zebrafish model. Keap1/Nrf2/ARE activator 2 can be used for the research of Alzheimer's disease.

Caricotamide (EP-0152R) is a coenzyme of quinone oxidoreductase 2 (NQO2). Caricotamide can efficiently induce the catalytic activity of NQO2 and enhance the anticancer activity of Tretazicar (HY-13543).

Glucoarabin is a bioactive glucosinolate. In Hepa1c1c7 cells, hydrolyzed Glucoarabin (hGSL 9) upregulates the phase II detoxification enzyme quinone reductase (NQO1), with no effect on cytochrome P450 (CYP) 1A1 activity.

Keap1-Nrf2-IN-30 is an orally active, blood-brain barrier-permeable Keap1-Nrf2 protein-protein interaction inhibitor with a Keap1 K_d value of 157 nM. Keap1-Nrf2-IN-30 selectively inhibits the Keap1-Nrf2 protein-protein interaction, promotes Nrf2 nuclear translocation, suppresses induced ferroptosis, reduces the expression of Aβ and p-Tau, and upregulates the expression of GPX4 and SLC7A11. Keap1-Nrf2-IN-30 upregulates the expression of HO-1 and NQO1, alleviates neuronal damage, and improves cognitive and spatial memory deficits. Keap1-Nrf2-IN-30 can be used in the research of Alzheimer's disease.

NQO2 activator-1 (Compound 1d) is a selective NQO2 activator with 20.89% increase of NQO2 activity at 10 μM. NQO2 activator-1 strongly inhibits NLRP3 inflammasome activation. NQO2 activator-1 can be used for the research of inflammation and immunology, such as rheumatoid arthritis.

Sesaminol is an orally active activator for Nrf2-ARE pathway, that promotes the the nuclear translocation of Nrf2 and enhances the NQO1 expression, thereby enhances the cell's defense against oxidative stress. Sesaminol inhibits 6-OHDA (HY-B1081)-induced ROS production and apoptosis in cell SH-SY5Y. Sesaminol exhibits neuroprotective efficacy against Rotenone (HY-B1756)-induced Parkinson's disease.

NFE2L2 activator 3 (Compound 3) is a NFE2L2/NRF2 activator. NFE2L2 activator 3 specifically activates the NAD(P)H:quinone oxidoreductase (NQO1) enzyme, with its EC₅₀ < 1 nM. NFE2L2 activator 3 can be used for research on respiratory system diseases such as chronic obstructive pulmonary disease.

KI696 (Standard) is the analytical standard of KI696 (HY-101140). This product is intended for research and analytical applications. KI696 is a selective KEAP1/NRF2 protein-protein interaction inhibitor with a human K_d value of 1.3 nM. KI696 acts by competitively occupying the NRF2-binding pocket of the KEAP1 Kelch domain. KI696 blocks KEAP1-mediated ubiquitination and degradation of NRF2, promotes the translocation of NRF2 to the nucleus, activates the expression of downstream antioxidant genes, increases intracellular glutathione levels, and alleviates oxidative stress-induced cell damage and inflammatory cell infiltration in the lungs. KI696 reduces ozone-induced pulmonary oxidative damage and inflammatory cell accumulation in rats, and upregulates pulmonary antioxidant genes. KI696 can be used in research related to chronic obstructive pulmonary disease, oxidative stress and inflammation.