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| Targets |
The primary target of deoxynyboquinone is NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme that is frequently overexpressed in various cancers. NQO1 is a two-electron reductase that catalyzes the reduction of quinones to hydroquinones, protecting cells from oxidative stress. Deoxynyboquinone is a substrate for NQO1, and its enzymatic reduction leads to the generation of reactive oxygen species (ROS) and oxidative stress. This redox cycling mechanism results in the production of superoxide and hydrogen peroxide, which cause mitochondrial dysfunction and induce apoptosis. The compound's selectivity for NQO1-overexpressing cancer cells makes it a promising agent for targeted cancer therapy. Tumors with defective antioxidant defenses are particularly sensitive to deoxynyboquinone-induced oxidative stress.
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| ln Vitro |
In cultured livers (SK-MEL-5, MCF-7, HL-60, and HL-60/ADR), deoxynyboquinone (DNQ; 72h) efficiently triggers mortality with IC50 values ranging from 16 to 210 nM [2]. Deoxynyboquine Through cytochrome c release during hypoxia, deoxynyboquinone (Group B1; 0.5 μM; 3, 6, 24 hours) effectively causes infrared death (HeLa cells; IC50: 5.1 μM) [2], HL-60) cell disinfection [3].
In vitro, deoxynyboquinone demonstrates potent anticancer activity against various cancer cell lines with IC₅₀ values ranging from 16 to 210 nM. The compound induces apoptosis in cancer cells through oxidative stress and the formation of reactive oxygen species (ROS). It is a substrate for NQO1, and its cytotoxicity is enhanced in cells with high NQO1 expression. Deoxynyboquinone is particularly effective against tumors with defective antioxidant defenses and high metabolic activity. Its unique mechanism of action involves mitochondrial disruption and ROS generation, making it effective against drug-resistant cancers. The compound's in vitro activity has been characterized using cell viability assays, ROS detection, and apoptosis assays in various cancer cell lines. |
| ln Vivo |
Deoxybenzoquinone (2.5, 5, and 10 mg/kg; injected five times a day, every week; intravenously shown on days 2–18) has anticancer effectiveness that is six times lower than beta Be-lapachone (30 mg/kg), as evidenced by overall survival (5 mg/kg)[4].
In vivo, deoxynyboquinone has demonstrated antitumor activity in preclinical models. As a substrate for NQO1, the compound generates ROS and induces oxidative stress in tumors with high NQO1 expression, leading to apoptosis and tumor regression. The compound's potential to target drug-resistant cancers and tumors with high metabolic activity makes it a promising candidate for further development. However, comprehensive in vivo efficacy studies in various tumor models, including xenografts and patient-derived xenografts, would be necessary to fully characterize the compound's antitumor activity. The compound's ability to target NQO1-overexpressing tumors suggests a favorable therapeutic index, as normal tissues typically have lower NQO1 expression. |
| Enzyme Assay |
In vitro enzyme assays for deoxynyboquinone measure its activity as a substrate for NQO1. In these assays, purified NQO1 enzyme is incubated with deoxynyboquinone and NAD(P)H as a cofactor. The reduction of deoxynyboquinone by NQO1 is monitored by measuring the consumption of NAD(P)H spectrophotometrically at 340 nm or by detecting the formation of the reduced product. The compound's ability to serve as a substrate for NQO1 is confirmed by the NAD(P)H-dependent reduction and the generation of ROS. These assays are essential for characterizing the compound's mechanism of action and for understanding its selectivity for NQO1-overexpressing cells.
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| Cell Assay |
In vitro cell-based assays for deoxynyboquinone evaluate its cytotoxic activity and mechanism of action in cancer cells. Cancer cell lines with varying levels of NQO1 expression are treated with varying concentrations of deoxynyboquinone, and cell viability is assessed using standard assays such as MTT, CellTiter-Glo, or sulforhodamine B. IC₅₀ values are determined from dose-response curves. ROS generation is measured using fluorescent probes such as DCFH-DA or dihydroethidium. Mitochondrial membrane potential is assessed using JC-1 dye, and apoptosis is quantified using Annexin V/PI staining or caspase activity assays. These assays confirm the compound's mechanism of action and provide functional data on its cellular activity.
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| Animal Protocol |
In vivo animal studies for deoxynyboquinone have been conducted in mouse models of cancer. In a typical study, immunocompromised mice are implanted with NQO1-overexpressing tumor cells to form subcutaneous xenografts. Once tumors reach a certain size, mice are randomized into treatment groups receiving deoxynyboquinone or vehicle control. Tumor volume and body weight are monitored regularly. At study endpoint, tumors are harvested for analysis of ROS levels, oxidative stress markers, and apoptosis. The compound's efficacy against drug-resistant tumors can be evaluated using cell lines that are resistant to standard chemotherapeutics. These studies are crucial for validating the therapeutic potential of deoxynyboquinone and for understanding its in vivo mechanism of action.
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| ADME/Pharmacokinetics |
Deoxynyboquinone has a molecular weight of approximately 244.20 g/mol. As a small-molecule quinone, it is a substrate for NQO1 and is expected to have reasonable drug-like properties. Detailed pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion are not extensively reported in the publicly available literature. The compound's metabolism would likely involve NQO1-mediated reduction and subsequent conjugation and excretion. Its ability to target NQO1-overexpressing tumors suggests that it may have favorable biodistribution properties for cancer therapy. However, comprehensive PK studies would be necessary to fully characterize the compound's ADME properties.
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| References |
[1]. Elizabeth I Parkinson, et al. Deoxynyboquinones as NQO1-Activated Cancer Therapeutics. Acc Chem Res. 2015 Oct 20;48(10):2715-23.
[2]. Joseph S Bair, et al. Chemistry and biology of deoxynyboquinone, a potent inducer of cancer cell death. J Am Chem Soc. 2010 Apr 21;132(15):5469-78. [3]. Tudor G, et,al. Cytotoxicity and apoptosis of benzoquinones: redox cycling, cytochrome c release, and BAD protein expression. Biochem Pharmacol. 2003;65(7):1061-1075. [4]. Huang X, et al. An NQO1 substrate with potent antitumor activity that selectively kills by PARP1-induced programmed necrosis. Cancer Res. 2012 Jun 15;72(12):3038-47. |
| Additional Infomation |
Deoxynyboqionone is a quinolone compound. It has been reported to exist in Streptomyces and Nocardia species, and relevant data are available for reference.
Deoxynyboquinone is a potent anticancer agent that induces oxidative stress and apoptosis in NQO1-overexpressing cancer cells. As a substrate for NQO1, the compound generates ROS and causes mitochondrial dysfunction. It is particularly effective against tumors with defective antioxidant defenses. The compound demonstrates IC₅₀ values ranging from 16 to 210 nM in cancer cell lines. It has potential for targeting drug-resistant cancers and tumors with high metabolic activity. Deoxynyboquinone is currently a research-grade compound and has not received FDA approval for any indication. |
| Molecular Formula |
C15H12N2O4
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|---|---|
| Molecular Weight |
284.271
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| Exact Mass |
284.079
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| CAS # |
96748-86-6
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| PubChem CID |
295934
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| Appearance |
Orange to red solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
591.2±50.0 °C at 760 mmHg
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| Flash Point |
311.4±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.659
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| LogP |
-0.41
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
21
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| Complexity |
778
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C2=C(C(=O)C3C(C)=CC(=O)NC=3C2=O)C(C)=CC1=O
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| InChi Key |
KJYPAIRTXRKKHG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H12N2O4/c1-6-4-8(18)16-12-10(6)14(20)11-7(2)5-9(19)17(3)13(11)15(12)21/h4-5H,1-3H3,(H,16,18)
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| Chemical Name |
1,4,6-trimethyl-9H-pyrido[3,2-g]quinoline-2,5,8,10-tetrone
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| Synonyms |
NSC 165572; DNQ; Deoxynyboquinone
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~4 mg/mL (~14.07 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5178 mL | 17.5889 mL | 35.1778 mL | |
| 5 mM | 0.7036 mL | 3.5178 mL | 7.0356 mL | |
| 10 mM | 0.3518 mL | 1.7589 mL | 3.5178 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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