NBDHEX
目录号 : GC39315
NBDHEX 是一种有效的谷胱甘肽 S-转移酶 P1-1 (GSTP1-1) 抑制剂。 NBDHEX 诱导肿瘤细胞凋亡。NBDHEX 通过抑制 GST 的催化活性，避免抑制剂被特异性泵从细胞中排出，以及破坏 GSTP1-1 和关键信号传导因子之间的相互作用，从而起到抗癌的作用。NBDHEX 也可以作为晚期自噬抑制剂。
Cas No.:787634-60-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
NBDHEX is a potent glutathione S-transferase P1-1 (GSTP1-1) inhibitor. NBDHEX induces apoptosis of tumor cells. NBDHEX acts as an anticancer agent by inhibiting GSTs catalytic activity, avoiding inconvenience of the inhibitor extrusion from the cell by specific pumps and disrupting the interaction between the GSTP1-1 and key signaling effectors. NBDHEX can also act as late-phase autophagy inhibitor[1][2].
[1]. Sha HH, et al. 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol: a promising new anticancer compound. Biosci Rep. 2018 Feb 13;38(1). pii: BSR20171440. [2]. Filomeni G, et al. 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol, a specific glutathione S-transferase inhibitor, overcomes the multidrug resistance (MDR)-associated protein 1-mediated MDR in small cell lung cancer. Mol Cancer Ther. 2008 Feb;7(2):371-9. [3]. Pellizzari Tregno F, et al. In vitro and in vivo efficacy of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on human melanoma. Eur J Cancer. 2009 Sep;45(14):2606-17.
| Cas No. | 787634-60-0 | SDF | |
| Canonical SMILES | OCCCCCCSC1=CC=C([N+]([O-])=O)C2=NON=C21 | ||
| 分子式 | C12H15N3O4S | 分子量 | 297.33 |
| 溶解度 | DMSO: 125 mg/mL (420.41 mM) | 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 | 3.3633 mL | 16.8163 mL | 33.6327 mL |
| 5 mM | 0.6727 mL | 3.3633 mL | 6.7265 mL |
| 10 mM | 0.3363 mL | 1.6816 mL | 3.3633 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
NBDHEX re-sensitizes adriamycin-resistant breast cancer by inhibiting glutathione S-transferase pi
Cancer Med 2023 Mar;12(5):5833-5845.PMID:36266920DOI:10.1002/cam4.5370.
Purpose: Adriamycin is a novel chemotherapeutic agent of great benefit for treating breast cancer. However, adriamycin -resistance remains a major obstacle. The vital Glutathione transferase P1 (GSTPi) inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) has recently shown antitumor activity in various cancers. In this study, we analyzed the effect of NBDHEX and adriamycin combination against breast cancer in vitro and in vivo. Methods: CCK-8 assay was performed to test cell viability. The location and expression level of GSTpi was determined by immunofluorescence and Western blot in cells and immunohistochemistry staining in tissues. The enzyme activity test was applied to detect the effect of NBDHEX on the activity of GSTpi. The apoptosis related proteins' expression was tested using Western blot. The phosphorylation sites of GSTpi were detected by mass spectrometry. Antitumor effects of single treatment or co-administration of adriamycin and NBDHEX were evaluated in nude mice. Results: NBDHEX treatment inhibited GSTpi enzyme activity and co-administration of adriamycin and NBDHEX promoted apoptosis of adriamycin-resistance breast cancer cell. Moreover, drug combination of NBDHEX and adriamycin significantly enhanced tumor growth inhibition compared with single agent. Conclusion: NBDHEX serves as a good candidate for combination with adriamycin, offering new insights for breast cancer treatment.
The Nitrobenzoxadiazole Derivative NBDHEX Behaves as Plasmodium falciparum Gametocyte Selective Inhibitor with Malaria Parasite Transmission Blocking Activity
Pharmaceuticals (Basel) 2022 Jan 29;15(2):168.PMID:35215282DOI:10.3390/ph15020168.
This work describes the activity of 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX) and of its newly identified carboxylic acid metabolite on the human malaria parasite Plasmodium falciparum. NBDHEX has been previously identified as a potent cytotoxic agent against murine and human cancer cells as well as towards the protozoan parasite Giardia duodenalis. We show here that NBDHEX is active in vitro against all blood stages of P. falciparum, with the rare feature of killing the parasite stages transmissible to mosquitoes, the gametocytes, with a 4-fold higher potency than that on the pathogenic asexual stages. This activity importantly translates into blocking parasite transmission through the Anopheles vector in mosquito experimental infections. A mass spectrometry analysis identified covalent NBDHEX modifications in specific cysteine residues of five gametocyte proteins, possibly associated with its antiparasitic effect. The carboxylic acid metabolite of NBDHEX retains the gametocyte preferential inhibitory activity of the parent compound, making this novel P. falciparum transmission-blocking chemotype at least as a new tool to uncover biological processes targetable by gametocyte selective drugs. Both NBDHEX and its carboxylic acid metabolite show very limited in vitro cytotoxicity on VERO cells. This result and previous evidence that NBDHEX shows an excellent in vivo safety profile in mice and is orally active against human cancer xenografts make these molecules potential starting points to develop new P. falciparum transmission-blocking agents, enriching the repertoire of drugs needed to eliminate malaria.
In Vitro and in Vivo Efficacy of NBDHEX on Gefitinib-resistant Human Non-small Cell Lung Cancer
J Cancer 2020 Oct 18;11(24):7216-7223.PMID:33193885DOI:10.7150/jca.46461.
Gefitinib, a first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), is recommended for treatment of non-small cell lung cancer (NSCLC) patients who harbor activating EGFR mutations. However, the tumors of most patients initially sensitive to gefitinib will develop resistance within several months of therapy. Drug resistance is a major obstacle to NSCLC treatment. The novel glutathione transferase P1 (GSTPi) inhibitor 6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) has recently been shown to be active against tumors. In this study, we investigated the in vitro and in vivo efficacy of NBDHEX against NSCLC. Treatment with NBDHEX inhibited GSTpi enzymatic activity and promoted apoptosis of gefinitb-resistant NSCLC cells. Moreover, NBDHEX reduced tumor growth in mice. These findings indicated that NBDHEX is a good candidate for treatment of NSCLC patients, and that NBDHEX offers a new approach to cancer therapy.
6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol: a promising new anticancer compound
Biosci Rep 2018 Feb 13;38(1):BSR20171440.PMID:29358310DOI:10.1042/BSR20171440.
The 7-nitro-2,1,3-nitrobenzoxadiazole (NBD) derivatives are a series of compounds containing the NBD scaffold that are not glutathione (GSH) peptidomimetics, and result in a strong inhibition of glutathione S-transferases (GSTs). Growing evidences highlight their pivotal roles and outstanding anticancer activity in different tumor models. In particular, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) is extensively studied, which is a very efficient inhibitor of GSTP1-1. It triggers apoptosis in several tumor cell lines and this cytotoxic activity is observed at micro and submicromolar concentrations. Importantly, studies have shown that NBDHEX acts as an anticancer drug by inhibiting GSTs catalytic activity, avoiding inconvenience of the inhibitor extrusion from the cell by specific pumps and disrupting the interaction between the GSTP1-1 and key signaling effectors. Additionally, some researchers also have discovered that NBDHEX can act as late-phase autophagy inhibitor, which opens new opportunities to fully exploit its therapeutic potential. In this review, we summarize the advantages, anticancer mechanisms, and analogs of this compound, which will establish the basis on the usage of NBDHEX in clinical applications in future.
In vitro and in vivo efficacy of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on human melanoma
Eur J Cancer 2009 Sep;45(14):2606-17.PMID:19665369DOI:10.1016/j.ejca.2009.06.033.
6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) is a powerful inhibitor of the glutathione transferase P1-1 (GSTP1-1) and causes the disruption of the complex between GSTP1-1 and c-Jun N-terminal Kinase (JNK). This induces JNK activation and apoptosis in tumour cells. In the present work we assess the in vitro and in vivo effectiveness of NBDHEX on two human melanoma cell lines, Me501 and A375. NBDHEX shows IC(50) values in the low micromolar range (IC(50) of 1.2+/-0.1microM and 2.0+/-0.2 microM for Me501 and A375, respectively) and is over 100 times more cytotoxic to these cell lines than temozolomide. Apoptosis is observed in Me501 cells within 3h of the addition of NBDHEX, while in A375 cells the apoptotic event is rather late, and is preceded by a G2/M phase arrest. In both melanoma cell lines, JNK activity is required for the ability of NBDHEX to trigger apoptosis, confirming that the JNK pathway is an important therapeutic target for this tumour. NBDHEX is also both effective and well tolerated in in vivo tumour models. A tumour inhibition of 70% is observed in vivo against Me501 human melanoma and a similar result is obtained on A375 model, with 63% of tumour inhibition. These findings indicate that the activation of the JNK pathway, through a selective GSTP1-1 targeting, could prove to be a promising new strategy for treating melanoma, which responds poorly to conventional therapies.