Deoxynyboquinone
目录号 : GC68306Deoxynyboquinone 是 NQO1 的底物，是有效的抗癌剂。Deoxynyboquinone 诱导癌症细胞凋亡 (Apoptosis)。Deoxynyboquinone 通过氧化应激和活性氧 (ROS) 的形成杀死癌细胞。
Cas No.:96748-86-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Deoxynyboquinone, an excellent NQO1 substrate, is a potent antineoplastic agent. Deoxynyboquinone induces Apoptosis in cancer cell lines. Deoxynyboquinone kills cancer cells through oxidative stress and reactive oxygen species (ROS) formation[1][2][3].
Deoxynyboquinone (DNQ; 72h) potently induces the death of cancer cells (SK-MEL-5, MCF-7, HL-60, HL-60/ADR) in culture, with IC50 values between 16 and 210 nM[2].
Deoxynyboquinone is still able to induce cancer cell death under hypoxic conditions (HeLa cell; IC50: 5.1 μM)[2].
Deoxynyboquinone (group B1; 0.5 μM; 3, 6, 24 hours) potently induces apoptosis in cancer cell lines (MCF-7, HL-60) through cytochrome c release[3].
Deoxynyboquinone (2.5, 5, and 10 mg/kg; every other day for 5 injections; i.v. for day 2-18) shows antitumor efficacy confirmed by overall survival (at 5 mg/kg), at a 6-fold lower dose than β-lapachone (30 mg/kg)[4].
[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.
| Cas No. | 96748-86-6 | SDF | Download SDF |
| 分子式 | C15H12N2O4 | 分子量 | 284.27 |
| 溶解度 | DMSO : 4 mg/mL (14.07 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
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动物平均体重 | g | |
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动物数量 | 只 |
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DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Pseudonocardia antitumoralis sp. nov., a deoxynyboquinone-producing actinomycete isolated from a deep-sea sediment
Int J Syst Evol Microbiol 2013 Mar;63(Pt 3):893-899.PMID:22634702DOI:10.1099/ijs.0.037135-0.
An aerobic actinomycete, designated SCSIO 01299(T), was isolated from a deep-sea sediment collected from the northern South China Sea at a depth of 3258 m. The isolate was found to be a natural producer of the synthesized antitumour agent Deoxynyboquinone and its three new derivatives, pseudonocardians A, B and C. A blast search based on almost-complete 16S rRNA gene sequences showed that strain SCSIO 01299(T) had high sequence similarities with members of the genus Pseudonocardia. The 16S rRNA gene sequence phylogenetic tree revealed that strain SCSIO 01299(T) was a member of the genus Pseudonocardia. Phenotypic analysis, chemotaxonomy and DNA-DNA relatedness could readily distinguish the isolate from established members in this genus. It was concluded that strain SCSIO 01299(T) represents a novel species, for which the name Pseudonocardia antitumoralis sp. nov. is proposed. The type strain is SCSIO 01299(T) ( = DSM 45322(T) = CCTCC M 2011255(T)).
Chemistry and biology of Deoxynyboquinone, a potent inducer of cancer cell death
J Am Chem Soc 2010 Apr 21;132(15):5469-78.PMID:20345134DOI:10.1021/ja100610m.
Deoxynyboquinone (DNQ) is a potent antineoplastic agent with an unknown mechanism of action. Here we describe a facile synthetic route to this anthraquinone, and we use this material to determine the mechanism by which DNQ induces death in cancer cells. DNQ was synthesized in seven linear steps through a route employing three palladium-mediated coupling reactions. Experiments performed on cancer cells grown in hypoxia and normoxia strongly suggest that DNQ undergoes bioreduction to its semiquinone, which then is re-oxidized by molecular oxygen, forming superoxide that induces cell death. Furthermore, global transcript profiling of cells treated with DNQ shows elevation of transcripts related to oxidative stress, a result confirmed at the protein level by Western blotting. In contrast to most other antineoplastic agents that generate reactive oxygen species (ROS), DNQ potently induces death of cancer cells in culture, with IC(50) values between 16 and 210 nM. In addition, unlike the experimental therapeutic elesclomol, DNQ is still able to induce cancer cell death under hypoxic conditions. This mechanistic understanding of DNQ will allow for a more comprehensive evaluation of the potential of direct ROS generation as an anticancer strategy, and DNQ itself has potential as a novel anticancer agent.
An NQO1 substrate with potent antitumor activity that selectively kills by PARP1-induced programmed necrosis
Cancer Res 2012 Jun 15;72(12):3038-47.PMID:22532167DOI:10.1158/0008-5472.CAN-11-3135.
Agents, such as β-lapachone, that target the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce programmed necrosis in solid tumors have shown great promise, but more potent tumor-selective compounds are needed. Here, we report that Deoxynyboquinone kills a wide spectrum of cancer cells in an NQO1-dependent manner with greater potency than β-lapachone. Deoxynyboquinone lethality relies on NQO1-dependent futile redox cycling that consumes oxygen and generates extensive reactive oxygen species (ROS). Elevated ROS levels cause extensive DNA lesions, PARP1 hyperactivation, and severe NAD+ /ATP depletion that stimulate Ca2+ -dependent programmed necrosis, unique to this new class of NQO1 "bioactivated" drugs. Short-term exposure of NQO1+ cells to Deoxynyboquinone was sufficient to trigger cell death, although genetically matched NQO1- cells were unaffected. Moreover, siRNA-mediated NQO1 or PARP1 knockdown spared NQO1+ cells from short-term lethality. Pretreatment of cells with BAPTA-AM (a cytosolic Ca2+ chelator) or catalase (enzymatic H2O2 scavenger) was sufficient to rescue deoxynyboquinone-induced lethality, as noted with β-lapachone. Investigations in vivo showed equivalent antitumor efficacy of Deoxynyboquinone to β-lapachone, but at a 6-fold greater potency. PARP1 hyperactivation and dramatic ATP loss were noted in the tumor, but not in the associated normal lung tissue. Our findings offer preclinical proof-of-concept for Deoxynyboquinone as a potent chemotherapeutic agent for treatment of a wide spectrum of therapeutically challenging solid tumors, such as pancreatic and lung cancers.
Efficient NQO1 substrates are potent and selective anticancer agents
ACS Chem Biol 2013 Oct 18;8(10):2173-83.PMID:23937670DOI:10.1021/cb4005832.
A major goal of personalized medicine in oncology is the identification of drugs with predictable efficacy based on a specific trait of the cancer cell, as has been demonstrated with gleevec (presence of Bcr-Abl protein), herceptin (Her2 overexpression), and iressa (presence of a specific EGFR mutation). This is a challenging task, as it requires identifying a cellular component that is altered in cancer, but not normal cells, and discovering a compound that specifically interacts with it. The enzyme NQO1 is a potential target for personalized medicine, as it is overexpressed in many solid tumors. In normal cells NQO1 is inducibly expressed, and its major role is to detoxify quinones via bioreduction; however, certain quinones become more toxic after reduction by NQO1, and these compounds have potential as selective anticancer agents. Several quinones of this type have been reported, including mitomycin C, RH1, EO9, streptonigrin, β-lapachone, and Deoxynyboquinone (DNQ). However, no unified picture has emerged from these studies, and the key question regarding the relationship between NQO1 processing and anticancer activity remains unanswered. Here, we directly compare these quinones as substrates for NQO1 in vitro, and for their ability to kill cancer cells in culture in an NQO1-dependent manner. We show that DNQ is a superior NQO1 substrate, and we use computationally guided design to create DNQ analogues that have a spectrum of activities with NQO1. Assessment of these compounds definitively establishes a strong relationship between in vitro NQO1 processing and induction of cancer cell death and suggests these compounds are outstanding candidates for selective anticancer therapy.
Airyscan super-resolution microscopy of mitochondrial morphology and dynamics in living tumor cells
Microsc Res Tech 2018 Feb;81(2):115-128.PMID:29131445DOI:10.1002/jemt.22968.
Mitochondrial morphology is regulated by continuous fusion-and-fission events that are essential for maintaining normal function. Despite the prominence of mitochondrial function in energy generation and cell signaling, understanding of processes of fusion and fission dynamics has been hampered by the lack of high-resolution optical systems that accommodate live-cell imaging. We have examined different confocal modalities in terms of resolution and signal-to-noise ratio (SNR) in a point scanning confocal microscope with Airyscan super-resolution (AS-SR). Results indicated that Airyscan (AS) provided speed, super-resolution, and high SNR. This modality was then used for monitoring mitochondrial dynamics in live tumor cells modified to harbor green-fluorescent protein localized to mitochondria. We then compared regular AS and fast-Airyscan modalities in terms of gentleness on the live-cell samples. The fast mode provided unprecedented imaging speed that permits monitoring dynamics both in 2D and also in three-dimensional dataset with time lapses (4D). Alterations to the mitochondrial network in U87 glioblastoma cells occurred within seconds and the cells were not affected by modest inhibition of fission. The super-resolution permitted quantitative measurements of mitochondrial diameter with a precision that enabled detection of significant differences in mitochondrial morphology between cell lines. We have observed swelling of mitochondrial tubules in A549 lung cancer cells after 2 hr treatment with Deoxynyboquinone, an ROS-generating pharmacologic drug. We also tested different 3D analytical parameters and how they can affect morphometric quantitation. The AS-SR imaging enabled high-speed imaging of mitochondrial dynamics without the compromise to cell morphology or viability that is common with conventional fluorescence imaging due to photo-oxidation.