| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
JHU-083 targets glutaminase, the enzyme that catalyzes the conversion of glutamine to glutamate. As a prodrug of the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON), JHU-083 is converted to the active DON moiety in vivo. DON irreversibly inhibits glutaminase, blocking glutamine metabolism. By inhibiting glutaminase, JHU-083 reduces glutamate production and modulates glutamine-dependent metabolic pathways in tumors and immune cells.
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| ln Vitro |
In vitro, JHU-083 functions as a glutaminase antagonist. The compound is a prodrug of 6-diazo-5-oxo-L-norleucine (DON), which irreversibly inhibits glutaminase. By blocking glutaminase activity, JHU-083 inhibits glutamine metabolism, which is essential for the proliferation of certain tumors and immune cells. These in vitro properties establish JHU-083 as a valuable tool for studying glutamine metabolism.
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| ln Vivo |
JHU-083 (1.82 mg/kg; face; once daily for 12 days) increases the behavior similar to anhedonia brought on by CSDS and reduces social avoidance [1]. Although it had minimal impact, JHU-083 (1.82 mg/kg; face) was able to distinguish between the elevations in forehead expression and glutaminase activity in hippocampus CD11b+ brain cells caused by CSDS. Treatment with JHU-083 can prevent the increase of TNF-α and IL-1β expression caused by CSDS [1].
In vivo, JHU-083 has been studied for its potential anti-depressive activity and for improving cognition in APOE4 mice. The compound blocks glutaminase activity in brain CD11b+ cells and prevents depression-associated behaviors induced by chronic social defeat stress. JHU-083 also improves cognition in APOE4 mice and normalizes abnormal hippocampal glutaminase activity. The compound has been studied in experimental cerebral malaria (ECM), resulting in a net decrease of glutamate levels. |
| Enzyme Assay |
JHU-083 is not typically used in standard receptor binding assays. Its activity is assessed through glutaminase enzyme inhibition assays or cell-based assays measuring glutamine metabolism. In enzyme inhibition assays, glutaminase activity is measured by monitoring the conversion of glutamine to glutamate. JHU-083 or its active metabolite DON is incubated with the enzyme and substrate at varying concentrations, and glutamate production is quantified. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
Cellular assays for JHU-083 are performed using cell lines that are dependent on glutamine metabolism for proliferation. Cells are cultured in appropriate media and treated with JHU-083 at varying concentrations for defined time periods. Cell viability and proliferation are assessed using standard assays such as MTT or CellTiter-Glo. Glutamine metabolism is assessed by measuring glutamine and glutamate levels in cell lysates or culture supernatant using HPLC or LC-MS.
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| Animal Protocol |
Animal/Disease Models: Male 7- to 8weeks old C57BL/6J (C57) mice (25-30 g) [1] with chronic social defeat stress (CSDS) [1]
Doses: 1.82 mg/kg Route of Administration: po (po (oral gavage)) Every other day for 12 days Experimental Results: Social avoidance behavior and anhedonia-like behavior caused by CSDS improved. In vivo studies with JHU-083 are conducted in animal models of depression, cognitive impairment, and cancer. JHU-083 is administered via oral routes at defined doses and schedules. For depression studies, behavioral assessments such as social defeat stress tests are performed. For cognitive studies, cognition is assessed using behavioral paradigms. Glutamate levels in brain tissues are measured by HPLC or LC-MS. Pharmacokinetic parameters are determined from plasma samples collected at various time points. |
| ADME/Pharmacokinetics |
JHU-083 has a molecular weight of 312.36 and a molecular formula of C14H24N4O4. The compound is a brain-penetrant prodrug of the glutamine antagonist DON. JHU-083 is soluble in DMSO at 60 mg/mL (192.08 mM). Solutions are unstable and should be fresh-prepared. Detailed pharmacokinetic parameters, including oral bioavailability and half-life, have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for JHU-083 are not extensively documented in publicly available sources. The compound is intended for research use only and is not approved for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety and chemical hygiene guidelines. The compound has a purity of ≥98%.
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| References |
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| Additional Infomation |
JHU-083 is a brain-penetrant prodrug of the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON), designed to inhibit glutamine metabolism in tumors and immune cells. It is an orally active and selective glutaminase antagonist. JHU-083 blocks glutaminase activity in brain CD11b+ cells and prevents depression-associated behaviors. The compound also improves cognition in APOE4 mice. JHU-083 is for research purposes only.
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| Molecular Formula |
C14H24N4O4
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|---|---|
| Molecular Weight |
312.3648
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| Exact Mass |
312.179
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| CAS # |
1998725-11-3
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| PubChem CID |
137283416
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
0.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
22
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| Complexity |
444
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C([C@@H](CC(C)C)N)N[C@@H](C(=O)OCC)CCC(C=[N+]=[N-])=O
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| InChi Key |
YZRCHOFKIPHQBW-VXGBXAGGSA-N
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| InChi Code |
InChI=1S/C14H24N4O4/c1-4-22-14(21)12(6-5-10(19)8-17-16)18-13(20)11(15)7-9(2)3/h8-9,11-12H,4-7,15H2,1-3H3,(H,18,20)/t11-,12-/m1/s1
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| Chemical Name |
Ethyl (R)-2-((R)-2-amino-4-methylpentanamido)-6-diazo-5-oxohexanoate
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| Synonyms |
JHU083 JHU 083 JHU-083
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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) |
Ethanol : ~133.33 mg/mL (~426.85 mM)
DMSO : ~100 mg/mL (~320.14 mM) H2O : ~50 mg/mL (~160.07 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2014 mL | 16.0072 mL | 32.0143 mL | |
| 5 mM | 0.6403 mL | 3.2014 mL | 6.4029 mL | |
| 10 mM | 0.3201 mL | 1.6007 mL | 3.2014 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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