6-diazo-5-oxo-L-nor-Leucine
(Synonyms: 6-重氮-5-氧代-L-正亮氨酸; L-6-Diazo-5-oxonorleucine; DON) 目录号 : GC412246-Diazo-5-oxo-L-nor-Leucine (DON)是一种抑制谷氨酰胺酶的谷氨酰胺类似物,是一种选择性的、基于机制的谷氨酰胺酶失活剂。
Cas No.:157-03-9
Sample solution is provided at 25 µL, 10mM.
6-Diazo-5-oxo-L-nor-Leucine (DON) is a glutamine analog that inhibits glutaminases, a selective, mechanism-based inactivator of glutamine-using enzymes[1-3].
6-Diazo-5-oxo-L-nor-Leucine(10-2µM-102µM ;48h) inhibited cell proliferation, and the inhibitory effect increased with the increase of concentration[4]. 6-Diazo-5-oxo-L-nor-Leucine (0.3 mM; 1 h) inhibited glutamine catabolism in WI-L2 cells[1].Treatment with 6-Diazo-5-oxo-L-nor-Leucine at 50 µM decreased colony formation in S2VP10 cells[5].
6-Diazo-5-oxo-L-nor-Leucine(1 mg/kg;5 days a week)decreased tumor progression as well as end-of-study tumor weight and volume[6].6-Diazo-5-oxo-l-norleucine as a Glutaminase(GLS) inhibitor that produces long lasting pain relief when applied to the inflamed paw of arthritic rats, DOX(2mM, 0.05ml;2times) can reduce the increase of the skin for vesicular transporters (VGluT2), GLS and glutamate immunoreactivity (IR) caused by surgery in a post-incisional model[7,8].
References:
[1]. Willis RC, Seegmiller JE. The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast. J Cell Physiol. 1977 Dec;93(3):375-82. doi: 10.1002/jcp.1040930308. PMID: 22551.
[2]. Thangavelu K, Pan CQ, et,al. Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7705-10. doi: 10.1073/pnas.1116573109. Epub 2012 Apr 26. PMID: 22538822; PMCID: PMC3356676.
[3]. Rais R, Lemberg KM, et,al. Discovery of DRP-104, a tumor-targeted metabolic inhibitor prodrug. Sci Adv. 2022 Nov 18;8(46):eabq5925. doi: 10.1126/sciadv.abq5925. Epub 2022 Nov 16. PMID: 36383674; PMCID: PMC9668306.
[4]. Leone RD, Zhao L, et,al. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science. 2019 Nov 22;366(6468):1013-1021. doi: 10.1126/science.aav2588. Epub 2019 Nov 7. PMID: 31699883; PMCID: PMC7023461.
[5]. Sharma NS, Gupta VK, et,al. Targeting tumor-intrinsic hexosamine biosynthesis sensitizes pancreatic cancer to anti-PD1 therapy. J Clin Invest. 2020 Jan 2;130(1):451-465. doi: 10.1172/JCI127515. PMID: 31613799; PMCID: PMC6934212.
[6]. Sharma NS, Gupta VK, et,al. Targeting tumor-intrinsic hexosamine biosynthesis sensitizes pancreatic cancer to anti-PD1 therapy. J Clin Invest. 2020 Jan 2;130(1):451-465. doi: 10.1172/JCI127515. PMID: 31613799; PMCID: PMC6934212.
[7]. Crosby HA, Miller KE. Evaluating the Analgesic Effect of the GLS Inhibitor 6-Diazo-5-Oxo-L-Norleucine in Vivo. Pharm Pharmacol Int J. 2016;3(3):00055. doi: 10.15406/ppij.2015.03.00055. Epub 2016 Jan 8. PMID: 29888760; PMCID: PMC5993434.
[8]. Miller KE, Hoffman EM, et,al. Glutamate pharmacology and metabolism in peripheral primary afferents: physiological and pathophysiological mechanisms. Pharmacol Ther. 2011 Jun;130(3):283-309. doi: 10.1016/j.pharmthera.2011.01.005. Epub 2011 Jan 26. PMID: 21276816; PMCID: PMC5937940.
6-Diazo-5-oxo-L-nor-Leucine (DON)是一种抑制谷氨酰胺酶的谷氨酰胺类似物,是一种选择性的、基于机制的谷氨酰胺酶失活剂[1-3]。
6-Diazo-5-oxo-L-nor-Leucine(10-2µM-102µM;48h)对细胞增殖有抑制作用,且抑制作用随浓度的增加而增强[4]。6-Diazo-5-oxo-L-nor-Leucine(0.3 mM;1 h)抑制WI-L2细胞谷氨酰胺分解代谢[1]。6-Diazo-5-oxo-L-nor-Leucine在50 µM下处理可减少S2VP10细胞的集落形成[5]。
6-Diazo-5-oxo-L-nor-Leucine (1 mg/kg,5 days a week)可降低肿瘤进展以及肿瘤的重量和体积[6]。6-Diazo-5-oxo-L-nor-Leucine作为谷氨酰胺酶抑制剂,应用于关节炎大鼠炎症足部,6-Diazo-5-oxo-L-nor-Leucine(2mM, 0.05ml;2times)可降低小鼠切口手术引起的皮肤中囊泡膜谷氨酸转运体、谷氨酰胺酶和谷氨酸免疫反应性(IR)的增加[7,8]。
| Cell experiment [1]: | |
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Cell lines |
MC38 cells |
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Preparation Method |
Tumor cells treated with increasing concentrations of 6-Diazo-5-oxo-L-nor-Leucine for 48h. |
|
Reaction Conditions |
10-2µM-102µM ;48h |
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Applications |
6-Diazo-5-oxo-L-nor-Leucine inhibited cell proliferation, and the inhibitory effect increased with the increase of concentration. |
| Animal experiment [2]: | |
|
Animal models |
Female athymic nude (nu/J) mice (pancreatic cancer cells S2VP10) |
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Preparation Method |
The tumors reached a size of 100 mm and were given to 6-Diazo-5-oxo-L-nor-Leucine at the end of the 4th week, and the mice were killed. |
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Dosage form |
1 mg/kg;5 days a week |
|
Applications |
Treatment with 6-Diazo-5-oxo-L-nor-Leucine decreased tumor progression as well as end-of-study tumor weight and volume. |
|
References: [1]. Leone RD, Zhao L, et,al. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science. 2019 Nov 22;366(6468):1013-1021. doi: 10.1126/science.aav2588. Epub 2019 Nov 7. PMID: 31699883; PMCID: PMC7023461. |
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| Cas No. | 157-03-9 | SDF | |
| 别名 | 6-重氮-5-氧代-L-正亮氨酸; L-6-Diazo-5-oxonorleucine; DON | ||
| 化学名 | 6-diazo-5-oxo-L-norleucine | ||
| Canonical SMILES | OC([C@@H](N)CCC(C=[N+]=[N-])=O)=O | ||
| 分子式 | C6H9N3O3 | 分子量 | 171.2 |
| 溶解度 | >1mg/mL in DMSO, >10mg/mL in Water(Need warm the tube at 50 ℃ and shake it in the ultrasonic bath for a while) | 储存条件 | Store at -20°C,protect from light, stored under nitrogen |
| 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 | 5.8411 mL | 29.2056 mL | 58.4112 mL |
| 5 mM | 1.1682 mL | 5.8411 mL | 11.6822 mL |
| 10 mM | 0.5841 mL | 2.9206 mL | 5.8411 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
