JHU395
Based on 1 Customer Validation
JHU395 is an orally active prodrug of 6-diazo-5-oxo-l-norleucine (HY-108357) and an antagonist of Glutamine amidotransferase. JHU395 blocks de novo purine synthesis, inhibits glutamine utilization, and induces Apoptosis. JHU395 exhibits antitumor activity. JHU395 can be used in research related to malignant peripheral nerve sheath tumors and MYC-driven medulloblastomas.
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- Purity: 99.69%
- CAS No.: 2079938-92-2
- 화학식: C22H29N3O7
- 분자량:447.48
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보관:Pure form -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
JHU395 (10 μM; 6 hours) significantly increases the relative abundance of PRPP and XMP in human sNF96.2 and JH-2-002 MPNST cells[1].
JHU395 (10 μM; 6 hours) reduces de novo purine synthesis in human sNF96.2 MPNST cells, as shown by a >25% reduction in 14C-glycine incorporation into DNA and RNA[1].
JHU395 (0.1-100 μM; 72 hours) partially inhibits growth of human sNF96.2, JH-2-002, and JH-2-031 MPNST cells with IC50 values of 3.48 μM, 2.40 μM, and 6.34 μM, respectively[1].
JHU395 (1 μM) partially inhibits colony formation in human JH-2-002 MPNST cells, and its inhibitory potency is enhanced when combined with 10 μM Pro-905, reducing colony formation by ~80%[1].
JHU395 (individual doses; 72 h) potently inhibits the growth of human sNF96.2 and sNF02.2 MPNST cells with IC50 values of 4.6 μM and 1.5 μM, respectively, while minimally affecting immortalized healthy ipn02.32λ Schwann cells; this growth inhibition is partially rescued by 100 μM guanosine monophosphate supplementation in sNF96.2 cells[2].
JHU395 (1-2 μM; 72 h) significantly reduces proliferation in D283MED and D425MED MYC-amplified medulloblastoma cell lines after 72 hours of treatment[3].
JHU395 potently inhibits the growth of high MYC human neural stem cells with an IC50 of 0.5 μM, which is 70-fold more potent than its activity against low MYC human neural stem cells (IC50 = 35 μM)[3].
JHU395 (20 μM; 1 h) delivers DON efficiently to human sNF96.2 MPNST cells in a plasma suspension, with 92% of total measured DON localized to cells after 1 hour of incubation with 20 μM JHU395[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human sNF96.2, JH-2-002, and JH-2-031 MPNST cells
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Concentration:0.1-100 μM
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Incubation Time:72 hours
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Result:Partially inhibited growth in all three MPNST cell lines with low micromolar IC50 values: 3.48 μM for sNF96.2, 2.40 μM for JH-2-002, and 6.34 μM for JH-2-031.
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Cell Line:human MYC-amplified medulloblastoma cell lines D283MED, D425MED
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Concentration:1-2 μM
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Incubation Time:72 h (JHU395); 6 h (BrdU)
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Result:Significantly reduced BrdU positivity, a marker of cell proliferation.
Decreased BrdU positivity of D283MED from 25% (vehicle) to 14.8% (1 μM) and 13.3% (2 μM; p < 0.001).
Decreased BrdU positivity of D425MED from 35.2% (vehicle) to 19.8% (1 μM) and 18.5% (2 μM; p < 0.001).
JHU395 (1.2 mg/kg; p.o.; 5 days per week; 12 days) reduces MPNST tumor growth, proliferation, and purine metabolite levels in a murine flank allograft model[1].
JHU395 (0.5-1.2 mg/kg; p.o.; daily; 14 days) significantly inhibits murine MPNST growth by 38.3% with no overt GI or neurotoxicity, while blocking glutamine utilization[2].
JHU395 (15 mg/kg; i.p.; twice weekly) significantly extends median survival of mice bearing orthotopic MYC-amplified medulloblastoma xenografts from 24 to 45 days, induces tumor-specific apoptosis, and causes only transient weight loss[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NPcis (B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J) (male and female)[1]
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Dosage:2.4 mg/kg
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Administration:p.o.; three times per week
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Result:Reduced tumor volume with a mean log fold change of 0.66 vs. vehicle's 2.60 (P = 0.045).
Slowed tumor growth over the first 30 days of dosing.
Extended median survival to 22 days vs. 12 days for vehicle (log rank P = 0.014).
Elevated formylglycinamide ribonucleotide (FGAR) levels and decreased inosine monophosphate (IMP) and guanosine monophosphate (GMP) levels in treated tumors.
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Animal Model:C57BL6/NHsd (B6) (male, ~10 weeks of age, 25-30 g)[1]
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Dosage:1.2 mg/kg
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Administration:p.o.; 5 days per week; 12 days
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Result:Reduced mean tumor volume to 1423 mm3 vs. 2225 mm3 for vehicle after 12 days of treatment.
Decreased tumor weight and mean mitotic rate score to 2 vs. 3 for vehicle.
Reduced mean Ki67-positive proliferation to 0.82% vs. 1.63% for vehicle.
Reduced tumor purine metabolites including dGMP and adenosylsuccinic acid.
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Animal Model:Nu/Nu (athymic nude) (female, orthotopic xenograft model via injection of 100,000 D425MED human MYC-amplified medulloblastoma cells into the cerebellum)[3]
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Dosage:15 mg/kg
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Administration:i.p.; twice weekly; starting day 10 after surgery
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Result:Extended median survival to 45 days (compared to 24 days for vehicle control, p < 0.001 by log-rank test).
Induced apoptosis (measured via cleaved-PARP expression) in orthotopic D425MED tumors 72 hours post-treatment.
Caused transient ~10% weight reduction at week 3 of treatment, followed by recovery to baseline before eventual weight loss due to tumor progression.
Chemical Information
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CAS No. 2079938-92-2
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Appearance Viscous Liquid
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분자량 447.48
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화학식 C22H29N3O7
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Color Colorless to light yellow
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SMILES
O=C(C(C)(C)C)OC(OC(N[C@@H](CCC(C=[N+]=[N-])=O)C(OC(C)C)=O)=O)C1=CC=CC=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Pure form -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : 100 mg/mL (223.47 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.59 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (287 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Lemberg KM, et al. Pro-905, a Novel Purine Antimetabolite, Combines with Glutamine Amidotransferase Inhibition to Suppress Growth of Malignant Peripheral Nerve Sheath Tumor. Molecular cancer therapeutics. 2023 Dec 01;22(12):1390-1403. [Content Brief]
[2]. Lemberg KM, et al. The Novel Glutamine Antagonist Prodrug JHU395 Has Antitumor Activity in Malignant Peripheral Nerve Sheath Tumor. Molecular cancer therapeutics. 2020 Feb;19(2):397-408. [Content Brief]
[3]. Pham K, et al. Novel Glutamine Antagonist JHU395 Suppresses MYC-Driven Medulloblastoma Growth and Induces Apoptosis. Journal of neuropathology and experimental neurology. 2021 Mar 22;80(4):336-344. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2347 mL | 11.1737 mL | 22.3474 mL | 55.8684 mL |
| 5 mM | 0.4469 mL | 2.2347 mL | 4.4695 mL | 11.1737 mL | |
| 10 mM | 0.2235 mL | 1.1174 mL | 2.2347 mL | 5.5868 mL | |
| 15 mM | 0.1490 mL | 0.7449 mL | 1.4898 mL | 3.7246 mL | |
| 20 mM | 0.1117 mL | 0.5587 mL | 1.1174 mL | 2.7934 mL | |
| 25 mM | 0.0894 mL | 0.4469 mL | 0.8939 mL | 2.2347 mL | |
| 30 mM | 0.0745 mL | 0.3725 mL | 0.7449 mL | 1.8623 mL | |
| 40 mM | 0.0559 mL | 0.2793 mL | 0.5587 mL | 1.3967 mL | |
| 50 mM | 0.0447 mL | 0.2235 mL | 0.4469 mL | 1.1174 mL | |
| 60 mM | 0.0372 mL | 0.1862 mL | 0.3725 mL | 0.9311 mL | |
| 80 mM | 0.0279 mL | 0.1397 mL | 0.2793 mL | 0.6984 mL | |
| 100 mM | 0.0223 mL | 0.1117 mL | 0.2235 mL | 0.5587 mL |
JHU395 Related Classifications
HY-128775 Related Classifications
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- JHU395
- 2079938-92-2
- JHU 395
- JHU-395
- Apoptosis
- phosphoribosyl pyrophosphate amidotransferase
- malignant peripheral nerve sheath tumors
- guanosine monophosphate synthetase
- D425MED medulloblastoma cell line
- sNF96.2 MPNST cells
- JH-2-002 MPNST cells
- D283MED medulloblastoma cell line
- phosphoribosyl formylglyinamidine amidotransferase
- de novo purine synthesis
- MYC-driven medulloblastoma
- Inhibitor
- inhibitor
- inhibit