Berzosertib (VE-822) is an ATR inhibitor with a Ki value of less than 0.2 nM. It also inhibits ATM with a Ki of 34 nM.
For research use only. We do not sell to patients.
Berzosertib Chemical Structure
CAS No. : 1232416-25-9
This product is a controlled substance and not for sale in your territory.
Based on 14 publication(s) in Google Scholar
Berzosertib purchased from MedChemExpress. Usage Cited in:
Eur J Med Chem. 2017 Feb 15;127:691-702.
[Abstract]
Relative cell viability (%) in MDCK CAIX- and CAIX+ cells exposed to ATR inhibitors (VE-821 and VE-822) or the CAIXi conjugated derivatives in combination with radiation during normoxia (21% O2) and anoxia (≤0.02% O2). Normoxic cells are irradiated with 2 Gy and anoxic cells with 4 Gy to induce similar effects on cell viability.
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ATM ATR
Description
Berzosertib (VE-822) is an ATR inhibitor with a Ki value of less than 0.2 nM. It also inhibits ATM with a Ki of 34 nM.
IC50 & Target[1]
ATR
0.2 nM (Ki)
ATM
34 nM (Ki)
PI3Kγ
220 nM (Ki)
In Vitro
Berzosertib (VE-822) also inhibits DNK-PA, mTOR, PI3Kγ with IC50 of >4, >1, and 0.22 μM, respectively. In PSN-1 and MiaPaCa-2 cells, Berzosertib (VE-822) inhibits ATR and ATM with IC50 of 19 nM and 2.6 μM, respectively. VE-822 (80 nM) reduces phospho-Ser345-Chk1 after NSC 613327 (100 nM), radiation (XRT) (6 Gy) or both in PDAC. Additionally, Berzosertib (VE-822) does not inhibit ATM, Chk2 or DNA-PK phosphorylation in response to radiation, which further supports the selectivity of Berzosertib (VE-822) for ATR. VE-822 decreases survival of irradiated PDAC (all lines used are p53-mutant; K-Ras mutant). Knock down of Chk1 by siRNA sensitizes PSN-1 and MiaPaCa-2 cells to radiation but the radiosensitising effect is less profound compare with Berzosertib (VE-822). Adding Berzosertib (VE-822) to NSC 613327 reduces survival ~2-3-fold and dramatically more after chemoradiotherapy[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Berzosertib Related Antibodies
In Vivo
PSN-1 xenografts are treated with Berzosertib (VE-822) (60 mk/kg; d0, 1), NSC 613327 (100 mg/kg; d0) and/or XRT (6 Gy; d1). Tumors are then harvested 2 h post-XRT. Berzosertib (VE-822) inhibits p-Ser-345-Chk1 in xenografts after DNA-damaging agents, establishing VE-822 as a potent inhibitor of ATR in vivo. Besides, Berzosertib (VE-822) enhances the therapeutic efficacy of radiation (XRT) in MiaPaCa-2 and PSN-1 xenograft models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
DMSO : ≥ 35 mg/mL (75.50 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.1573 mL
10.7863 mL
21.5726 mL
5 mM
0.4315 mL
2.1573 mL
4.3145 mL
10 mM
0.2157 mL
1.0786 mL
2.1573 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, 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.
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: ≥ 2.5 mg/mL (5.39 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 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% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.39 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO 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.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. 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% Vitamin E-TPGS in Saline
Solubility: 9.38 mg/mL (20.24 mM); Suspended solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (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.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
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.
[1]. Fokas E, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441.
[Content Brief]
Cell Assay
[1]
NSC 613327 (10 nM) is added 24 h pre-XRT and is replaced with fresh medium before addition of Berzosertib (VE-822). PSN-1 cells are treated with Berzosertib (VE-822) (80 nM) for 1 h before, through to 18 h after, XRT (6 Gy). Apoptosis is analyzed 48 h after XRT by flow cytometry using an Annexin V-FITC kit with PI[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]
Mice[1] MiaPaCa-2 cells and PSN-1 cells (106 in 50 μL serum-free medium mixed with 50 μL of Matrigel) are inoculated subcutaneously in female Balb/c nude mice. When the xenograft tumors reach 80 mm3, the mice are randomized. Berzosertib (VE-822) (60 mg/kg) is administered by oral gavage on one of three alternate schedules; either daily on days 0-5 (total of six days dosing), daily on days 0 through to 3 (total of 4 days dosing) or on days 1, 3 and 5. XRT (6 Gy) is given either on days 0 or 1 or days 1-5 (total of 5 days dosing; 2 Gy). NSC 613327 is dosed at 100 mg/kg by intraperitoneal injection on day 0. XRT to the tumor is given 2 h after initiation of Berzosertib (VE-822) treatment.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References
[1]. Fokas E, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441.
[Content Brief]
[1]. Fokas E, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441.
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
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
2.1573 mL
10.7863 mL
21.5726 mL
53.9316 mL
5 mM
0.4315 mL
2.1573 mL
4.3145 mL
10.7863 mL
10 mM
0.2157 mL
1.0786 mL
2.1573 mL
5.3932 mL
15 mM
0.1438 mL
0.7191 mL
1.4382 mL
3.5954 mL
20 mM
0.1079 mL
0.5393 mL
1.0786 mL
2.6966 mL
25 mM
0.0863 mL
0.4315 mL
0.8629 mL
2.1573 mL
30 mM
0.0719 mL
0.3595 mL
0.7191 mL
1.7977 mL
40 mM
0.0539 mL
0.2697 mL
0.5393 mL
1.3483 mL
50 mM
0.0431 mL
0.2157 mL
0.4315 mL
1.0786 mL
60 mM
0.0360 mL
0.1798 mL
0.3595 mL
0.8989 mL
Berzosertib Related Classifications
Cell Cycle/DNA DamagePI3K/Akt/mTOR
ATM/ATR
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:
Berzosertib1232416-25-9VE-822 VX-970VE822VE 822VX970VX 970VX-970ATM/ATRAtaxia telangiectasia mutatedATM and RAD3 relatedInhibitorinhibitorinhibit
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