VX-984
Based on 4 publication(s) in Google Scholar
VX-984 is an orally active, potent, selective and BBB-penetrated DNA-PK inhibitor. VX-984 efficiently inhibits NHEJ (non-homologous end joining) and increases DSBs (DNA double-strand breaks). VX-984 can be used for glioblastomas (GBM) and non-small cell lung cancer (NSCLC) research. VX-984 is a de novo deuterium.
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- Pureté: 99.47%
- CAS No.: 1476074-39-1
- Formule: C23H21D2N7O
- Masse moléculaire:415.49
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) VX-984
More
Activité biologique
VX-984 (0-500 nM, 30 min) inhibits radiation-induced DNA-PKcs phosphorylation in U251 and NSC11 cells[1].
VX-984 (0-500 nM) enhances the radiosensitivity of U251 and NSC11 cells in a concentration-dependent manner[1].
VX-984 inhibits the repair of radiation-induced DNA double-strand breaks (DSBs)[1].
VX-984 (0-1 μM) increases alternate pathways of DSB repair, including HR (homologous recombination) and mutagenic NHEJ (mNHEJ)[2].
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[4].
Potential advantages of deuterated compounds:
(1) Extend the half-life in vivo. Deuterated compounds may be able to prolong the pharmacokinetic characteristics of the compound, that is, prolong the half-life in vivo. This can improve compound safety, efficacy and tolerability, and increase ease of administration.
(2) Improve oral bioavailability. Deuterated compounds may reduce the degree of unwanted metabolism (first-pass metabolism) in the gut wall and liver, allowing a greater proportion of the unmetabolized drug to reach its target site of action. High bioavailability determines its activity at low doses and better tolerance.
(3) Improve metabolic characteristics. Deuterated compounds may reduce the formation of toxic or reactive metabolites and improve drug metabolism.
(4) Improve drug safety. Deuterated compounds may reduce or eliminate adverse side effects of pharmaceutical compounds and are safe.
(5) Preserve the therapeutic properties. Deuterated compounds are expected to retain similar biochemical potency and selectivity to hydrogen analogs in previous studies.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:U251 and NSC11 cells
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Concentration:0, 100, 250, and 500 nM
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Incubation Time:30 min
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Result:Showed a concentration-dependent decrease in radiation-induced DNA-PKcs phosphorylation in each glioma line, when VX-984 was delivered 1 hour before irradiation. VX-984 treatment alone had no effect.
VX-984 (0-50 mg/kg, Oral gavage, twice a day for 2 days) enhances the radiosensitivity of brain tumor xenografts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Athymic female nude mice (6-8 weeks old, 7-8 mice/group, U251 intracerebral xenografts)[1]
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Dosage:0, 50, and 100 mg/kg
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Administration:Oral gavage, daily, 1 or 4 hours before irradiation (10 Gy)
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Result:Reduced the levels DNA-PKcs phosphorylation after irradiation.
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Animal Model:Athymic female nude mice (6-8 weeks old, 7 mice/group, U251 intracerebral xenografts)[1]
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Dosage:0, 50 mg/kg
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Administration:Oral gavage, twice a day, 30 minutes before and 4 hours following local irradiation of the tumor (3 Gy) for 3 consecutive days (3×3 Gy)
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Result:VX-984 treatment of U251 tumors alone had no significant effect on overall survival as compared with vehicle; radiation alone resulted in an increase in survival. VX-984 and radiation combination protocol increased tumor radiosensitivity, and significantly increased the survival of mice compared with radiation alone.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
1. This compound can be used as a tracer
2. This compound can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS.
Chemical Information
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CAS No. 1476074-39-1
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Unlabeled Cas 1476071-49-4
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Appearance Solid
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Masse moléculaire 415.49
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Formule C23H21D2N7O
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Color White to off-white
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SMILES
O=C(C1=CC=NC2=C([C@H](C)CNC3=CC(C4=C([2H])N=C(C)N=C4[2H])=NC=N3)C=CC=C12)NC
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Synonyms
M9831
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (4)
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Journal Impact Factor
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Most Recent
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Nat Biotechnol
High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition. [Abstract]2024 May;42(5):731-744. PMID: 37537500 -
Nat Commun
A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo. [Abstract]2023 Sep 6;14(1):5474. PMID: 37673883 -
Cell Death Dis
Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs. [Abstract]2020 Jul 30;11(7):602. PMID: 32732911 -
Transl Oncol
UAE1 inhibition mediates the unfolded protein response, DNA damage and caspase-dependent cell death in pancreatic cancer. [Abstract]2020 Nov;13(11):100834. PMID: 32688248
Solvant et solubilité
DMSO : 10 mg/mL (24.07 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1 mg/mL (2.41 mM); Clear solution
This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
Pureté et documentation
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Fiche technique (282 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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Instruction de manipulation (2659 KB)
Références
[1]. Timme CR, et al. The DNA-PK Inhibitor VX-984 Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and as Orthotopic Xenografts. Mol Cancer Ther. 2018 Jun;17(6):1207-1216. [Content Brief]
[2]. Khan AJ, et al. VX-984 is a selective inhibitor of non-homologous end joining, with possible preferential activity in transformed cells. Oncotarget. 2018 May 25;9(40):25833-25841. [Content Brief]
[4]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. [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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4068 mL | 12.0340 mL | 24.0680 mL | 60.1699 mL |
| 5 mM | 0.4814 mL | 2.4068 mL | 4.8136 mL | 12.0340 mL | |
| 10 mM | 0.2407 mL | 1.2034 mL | 2.4068 mL | 6.0170 mL | |
| 15 mM | 0.1605 mL | 0.8023 mL | 1.6045 mL | 4.0113 mL | |
| 20 mM | 0.1203 mL | 0.6017 mL | 1.2034 mL | 3.0085 mL |
VX-984 Related Classifications
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