2. Cell Cycle/DNA Damage PI3K/Akt/mTOR
  3. DNA-PK
  4. VX-984

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.

For research use only. We do not sell to patients.

VX-984 Chemical Structure

VX-984 Chemical Structure

CAS No. : 1476074-39-1

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 605 In-stock
Solution
10 mM * 1 mL in DMSO USD 605 In-stock
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10 mg USD 950 In-stock
50 mg USD 3950 In-stock
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Based on 4 publication(s) in Google Scholar

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VX-984 Related Antibodies

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  • Purity & Documentation

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Description

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[1][2][3].

In Vitro

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.

VX-984 Related Antibodies

Western Blot Analysis[1]

Cell Line: U251 and NSC11 cells
Concentration: 0, 100, 250, and 500 nM
Incubation Time: 30 min
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.
In Vivo

VX-984 (0-100 mg/kg, Oral gavage, daily) inhibits radiation-induced DNA-PKcs phosphorylation in orthotopic brain tumor xenografts[1].
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.

Animal Model: Athymic female nude mice (6-8 weeks old, 7-8 mice/group, U251 intracerebral xenografts)[1]
Dosage: 0, 50, and 100 mg/kg
Administration: Oral gavage, daily, 1 or 4 hours before irradiation (10 Gy)
Result: Reduced the levels DNA-PKcs phosphorylation after irradiation.
Animal Model: Athymic female nude mice (6-8 weeks old, 7 mice/group, U251 intracerebral xenografts)[1]
Dosage: 0, 50 mg/kg
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)
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.
Clinical Trial
Molecular Weight

415.49

Formula

C23H21D2N7O
CAS No.
Unlabeled CAS

1476071-49-4
Appearance

Solid

Color

White to off-white

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.4068 mL 12.0340 mL 24.0680 mL
5 mM 0.4814 mL 2.4068 mL 4.8136 mL
View the 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.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

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.

  • Protocol 1

    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.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 1 mg/mL (2.41 mM); Clear solution

    This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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(per animal)

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(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
Purity & Documentation

Purity: 98.86%

COA (251 KB) HNMR (203 KB) RP-HPLC (111 KB) LCMS (128 KB)

Handling Instructions (2659 KB)
References

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
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VX-984 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

VX-9841476074-39-1M9831VX984VX 984M 9831M-9831DNA-PKDNA-dependent protein kinaseU251NSC11non-homologous end joiningglioblastomasDNA repairradiationNSCLCγ-H2AXInhibitorinhibitorinhibit

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