nqo1

NQO1 substrate is a highly potent NQO1 substrate with potential antitumor activity for leukemia research.

Dicoumarol (Dicumarol) is a hydroxycoumarin originally isolated from molding sweet-clover hay, with anticoagulant and vitamin K depletion activities. Dicoumarol is a competitive inhibitor of vitamin K epoxidereductase; thus, it inhibits vitamin K recycling and causes depletion of active vitamin K in blood. This prevents the formation of the active form of prothrombin and several other coagulant enzymes, and inhibits blood clotting.

KL1333 (NQO1 activator 1) enhances energy metabolism and mitochondrial dysfunction in MELAS fibroblasts. Elevated NAD+ levels trigger the activation of SIRT1 and AMPK, and subsequently activates PGC-1α. NQO1 activator 1 is an orally available NAD+ modulator. It reacts with NAD(P)H: NQO1 as a substrate, resulting in increases in intracellular NAD+ levels via NADH oxidation.

CB1954(Tretazicar (NSC-115829)), an anticancer prodrug, is activated by NAD(P)H quinone oxidoreductase 2. It is converted in the presence of the enzyme NQO2 and co-substrate caricotamide ( EP-0152R) (EP) into a potent cytotoxic bifunctional alkylating agent.

2-HBA, a synthetic analog of curcumin, is an indirect inducer of enzymes that catalyze detoxification reactions through the Keap1-Nrf2-ARE pathway.

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.

Keap1-Nrf2-IN-24 (compound 57) is an effective Keap1-Nrf2 inhibitor with a Ki value of 13 nM. This compound enhances the protein expression of TRXR1 and NQO1, as well as the mRNA expression of AKR1B10. Additionally, Keap1-Nrf2-IN-24 demonstrates good metabolic stability.

Sesaminol is an orally active activator of the Nrf2-ARE signaling pathway, promoting the nuclear translocation of Nrf2 and boosting the expression of NQO1 to enhance cellular defense against oxidative stress. It inhibits 6-OHDA-induced ROS production and apoptosis in SH-SY5Y cells. Sesaminol also provides neuroprotective effects against Rotenone-induced Parkinson's disease.

Keap1-IN-1 (Compound 27) is an inhibitor of Keap1, functioning by covalently modifying the Cys151 residue on the BTB domain of KEAP1, thereby disrupting the interaction between Keap and Nrf. It enhances the mRNA expression of the antioxidant response element (ARE) dependent gene NQO1, with an EC50 of 160 nM, and exhibits cytotoxicity in U2OS cells, with an EC50 of 527 nM.

NSC 645827 is an inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1), with an IC50 of 0.7 μM.

Antitumor agent-195 (compound 16c) is a dual-targeting agent that simultaneously targets STAT3 and NQO1. At a concentration of 1 μM, it significantly inhibits the phosphorylation of STAT3 at the Tyr705 site and effectively induces apoptosis in MDA-MB-231 and MDA-MB-468 breast cancer cells. As a substrate of NQO1, Antitumor agent-195 markedly increases ROS production, causing severe DNA damage in a dose-dependent manner. It also demonstrates strong antitumor properties in MDA-MB-231 xenograft models.

N-Benzyl-N-demethylpronqodine A serves as an inhibitor of NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), exhibiting an IC50 value of 83.3 nM.

ES 936 is a potent and selective NQO1 inhibitor, inhibiting more than 95% of NQO1 activity within 30 minutes at a concentration of 100 nM, with a cell line-dependent inhibition duration resulting in a small number of DNA strand breaks.

Diminutol is a cell-permeable purine derivative that inhibits the NADP-dependent oxidoreductase, NQO1 (Ki = 1.72 μM), to destabilize microtubules and disrupt mitosis. At 50 μM, it directly affects tubulin polymerization in Xenopus egg extracts without interfering with the activity of Cdk1, DNA replication, or actin polymerization.

Isobutyl-deoxynyboquinone (IB-DNQ) is a selective substrate for NAD(P)H:quinone oxidoreductase [NQO1] and is utilized in anticancer research.

1. 5,7-Dihydroxychromone (5,7-Dihydroxy-4H-Chromen-4-One) isolated from DME is one of the active compounds that may contribute to regulate blood glucose levels. 2. 5,7-Dihydroxychromone exerts neuroprotective effect against 6-OHDA-induced oxidative stress and apoptosis by activating Nrf2/ARE signal . 3. 5,7-Dihydroxychromone induces the translocation of Nrf2 to the nucleus and increases Nrf2/ARE binding activity which results in the up-regulation of the expression of Nrf2-dependent antioxidant genes, including HO-1, NQO1, and GCLc.

Antitumor agent-57 (Compound 3o) is a potent NQO1-directed antitumor compound that effectively inhibits tumor cell growth, induces ROS generation, and promotes cell apoptosis [1].

Nampt-IN-8 is a NAMPT inhibitor (IC50: 0.183 μM) and a good substrate for NQO1. Nampt-IN-8 induces reactive oxygen species (ROS) production and apoptosis.

1. Geraniin has a protective effect against OVX-induced rat osteoporosis. 2. Geraniin has cytotoxic activity towards cancer cells in vitro and in vivo. 3. Geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle

Keap1-Nrf2-IN-10 (compound 15) is a potent inducer of NQO1 that effectively mitigates oxidative stress in gamma-irradiated mice by reducing MDA and ROS levels, and NQO1 in the liver, thereby enhancing survival rates [1].

Glucoarabin, a bioactive glucosinolate, upregulates the phase II detoxification enzyme quinone reductase (NQO1) in Hepa1c1c7 cells when hydrolyzed (hGSL 9), without affecting cytochrome P450 (CYP) 1A1 activity [1].

Antitumor agent-67 (compound 3), a potent antitumor agent, exhibits highly selective toxicity toward cancer cells while sparing normal cells. This compound can be activated by NQO1 to effectively release podophyllotoxin, thereby killing tumor cells. In HepG2 xenograft models, Antitumor agent-67 significantly inhibits cancer growth with minimal toxicity [1].

Fraxinellone analog 1 (compound 2) is an effective and rapid activator of the Nrf2-mediated antioxidative defense system, providing protection against glutamate-mediated excitotoxicity. It induces the expression of antioxidative genes Gpx4, Sod1, and Nqo1. Additionally, Fraxinellone analog 1 exerts neuroprotective effects and modulates oxidative stress and inflammation, making it suitable for research on neurodegenerative diseases.

Pronqodine A is a quinone isolated from Streptomyces, known for its enzyme inhibitory and anti-inflammatory properties. It targets NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1; IC50 = 131.5 nM). In SW 982 human synovial sarcoma cells, it suppresses bradykinin-induced production of prostaglandin E2 (PGE2), 6-keto PGF1α, and PGD2, with IC50 values of 9, 19, and 7 nM, respectively, and it also promotes the generation of reactive oxygen species (ROS) in these cells.