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6-diazo-5-oxo-L-nor-Leucine (Synonyms: DON, NSC 7365)

Catalog No.GC41224

La 6-Diazo-5-oxo-L-nor-Leucine (DON) est un analogue de la glutamine qui inhibe les glutaminases, un inactivateur sélectif et basé sur le mécanisme des enzymes utilisant la glutamine[1-3].

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6-diazo-5-oxo-L-nor-Leucine Chemical Structure

Cas No.: 157-03-9

Taille Prix Stock Qté
5mg
67,00 $US
En stock
10mg
126,00 $US
En stock
25mg
291,00 $US
En stock
50mg
521,00 $US
En stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

MC38 cells

Preparation Method

Tumor cells treated with increasing concentrations of 6-Diazo-5-oxo-L-nor-Leucine for 48h.

Reaction Conditions

10-2µM-102µM ;48h

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)

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.

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.
[2].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.

Background

La 6-Diazo-5-oxo-L-nor-Leucine (DON) est un analogue de la glutamine qui inhibe les glutaminases, un inactivateur sélectif et basé sur le mécanisme des enzymes utilisant la glutamine[1-3].

La 6-Diazo-5-oxo-L-nor-Leucine (10-2µM-102µM ;48h) a inhibé la prolifération cellulaire, et l'effet inhibiteur a augmenté avec l'augmentation de la concentration[4]. La 6-Diazo-5-oxo-L-nor-Leucine (0,3 mM; 1 h) a inhibé le catabolisme de la glutamine dans les cellules WI-L2[1]. Le traitement avec la 6-Diazo-5-oxo-L-nor-Leucine à 50 µM a diminué la formation de colonies dans les cellules S2VP10[5].

La L-nor-leucine 6-diazo-5-oxo (1 mg/kg ; 5 jours par semaine) a réduit la progression tumorale ainsi que le poids et le volume de la tumeur à la fin de l'étude[6]. En tant qu'inhibiteur de la glutaminase (GLS), elle produit un soulagement durable de la douleur lorsqu'elle est appliquée sur la patte enflammée des rats arthritiques. Le DOX (2 mM, 0,05 ml ; 2 fois) peut réduire l'augmentation des transporteurs vésiculaires (VGluT2), GLS et immunoréactivité au glutamate (IR) causée par une intervention chirurgicale dans un modèle post-incisionnel[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.

Chemical Properties

Cas No. 157-03-9 SDF
Synonymes DON, NSC 7365
Chemical Name 6-diazo-5-oxo-L-norleucine
Canonical SMILES OC([C@@H](N)CCC(C=[N+]=[N-])=O)=O
Formula C6H9N3O3 M.Wt 171.2
Solubility >1mg/mL in DMSO, >10mg/mL in Water(Need warm the tube at 50 ℃ and shake it in the ultrasonic bath for a while) Storage Store at -20°C,protect from light, stored under nitrogen
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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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
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Average Rating: 5 ★★★★★ (Based on Reviews and 20 reference(s) in Google Scholar.)

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