Cat. No.: HY-13902A

Berzosertib hydrochloride

(Synonyms: VE-822 hydrochloride; VX-970 hydrochloride; M6620 hydrochloride)

26 Cited Publications

Customer Review

Based on 26 publication(s) in Google Scholar

Berzosertib (VE-822) hydrochloride is an orally active, CNS-penetrant, and selective ATR kinase inhibitor. Berzosertib hydrochloride blocks ATR kinase activity, abrogates G₂/M cell cycle checkpoint, impairs DNA damage repair. Berzosertib hydrochloride induces apoptosis, inhibnits conlony migration, inhibits cell proliferation, and activates cGAS-STING axes in cancer cells. Berzosertib hydrochloride can be used for the research of cancers, such as head and neck squamous cell carcinoma, and colorectal cancer.

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

Purity: 98.77%
CAS No.: 1428935-04-9
Formula: C₂₄H₂₆ClN₅O₃S
Molecular Weight:500.01

Storage:

4°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Berzosertib hydrochloride Chemical Structure

CAS No.: 1428935-04-9

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Publications (26)
Purity & Documentation
References
Calculators
Help & FAQs
Bioz

Biological Activity

Description

IC₅₀ & Target^[1]

Caspase-3

ATR

0.2 nM (Ki)

ATM

34 nM (Ki)

All ATM/ATR Isoforms :

All Caspase Isoforms :

In Vitro

Berzosertib (0.031-1 µM; 72 h) hydrochloride reduces cell viability in Cal-27 and FaDu HNSCC cell lines with IC₅₀ values of 0.285 µM and 0.252 µM, respectively^[1].
Berzosertib (0.125-0.5 µM; 24-48 h) hydrochloride inhibits migration in Cal-27 and in FaDu HNSCC cells^[1].
Berzosertib (0.25-0.5 µM; 48 h) hydrochloride induces apoptosis in Cal-27 and FaDu cells^[1].
Berzosertib (48-72 h) hydrochloride inhibits proliferation of A549, NCI-H226, and NCI-H520 cells with IC₅₀ values in the 1-4 μM range^[2].
Berzosertib (40-80 nM; 1 h) hydrochloride enhances radiosensitivity of A549, NCI-H226, and NCI-H520 NSCLC cell lines^[2].
Berzosertib (40 nM; 1 h) hydrochloride inhibits radiation-induced ATR (Thr1989) phosphorylation in A549, NCI-H226, and NCI-H520 NSCLC cell lines without affecting ATM (Ser1981) activation^[2].
Berzosertib (40 nM; 1 h) hydrochloride abrogates the radiation-induced G₂/M cell cycle checkpoint in A549 NSCLC cells, shifting cells into G₁ phase^[2].
Berzosertib (40-80 nM; 1 h) hydrochloride enhances radiation-induced apoptosis in A549 NSCLC cells when combined with 10 Gy, but not 2 Gy, irradiation^[2].
Berzosertib (40 nM; 1 h) hydrochloride inhibits DNA double-strand break repair in A549 cells^[2].
Berzosertib (1 µM; 2 h) hydrochloride impairs irradiation-induced G₂/M checkpoint initiation and maintenance in HCT116 and CT26 cells, promoting mitotic entry after DNA damage^[4].
Berzosertib (1 µM; 2 h) hydrochloride combined with 5 Gy irradiation increases micronuclei formation and cytosolic dsDNA levels in HCT116 and CT26 colorectal cancer cell lines^[4].
Berzosertib (1 µM; 2 h) hydrochloride combined with 5 Gy irradiation robustly activates the canonical cGAS-STING-pTBK1/pIRF3 pathway, and upregulates expression of interferon-stimulated genes CXCL10, CCL5, and IFNB in HCT116, SW480, CT26, and MC38 cells^[4].
Berzosertib (1 µM; 2 h) hydrochloride combined with 5 Gy irradiation inhibits the recruitment of SHP1 to the TRAF6/STING complex in HCT116 cells, enhancing TRAF6-STING interaction^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[1]

Cell Line:

Cal-27, FaDu cells
Concentration:

0.031; 0.063; 0.125; 0.25; 0.5; 1 µM
Incubation Time:

72 h
Result:

Caused a dose-dependent decrease in cell viability in both cell lines.
Exhibited an IC₅₀ value of 0.285 µM for Cal-27 cells.
Exhibited an IC₅₀ value of 0.252 µM for FaDu cells.

Cell Proliferation Assay^[1]

Cell Line:

Cal-27, FaDu cells
Concentration:

0.125; 0.25; 0.5 µM
Incubation Time:

24 h (Cal-27); 48 h (FaDu)
Result:

Reduced Cal-27 cell gap closure to 82% at 0.25 µM and 50% at 0.5 µM at 24 h, compared to 98% in untreated cells.
Reduced FaDu cell gap closure to 24% at 0.25 µM and 0.5 µM at 24 h, compared to 41% in untreated cells.
Significantly inhibited FaDu cell gap closure at 0.5 µM at 48 h.

Apoptosis Analysis^[1]

Cell Line:

Cal-27, FaDu cells
Concentration:

0.25 µM (Cal-27); 0.5 µM (FaDu)
Incubation Time:

48 h
Result:

Increased apoptosis levels to 279% of control in Cal-27 cells.
Increased apoptosis levels to 244% of control in FaDu cells.

Western Blot Analysis^[2]

Cell Line:

A549, NCI-H226, and NCI-H520 cells
Concentration:

40 nM
Incubation Time:

1 h
Result:

Did not affect radiation-induced ATM (Ser1981) phosphorylation.
Diminished radiation-induced activation of p-ATR (Thr1989) in all three cell lines even at 24 h post-radiation.

Apoptosis Analysis^[2]

Cell Line:

A549 cells
Concentration:

40; 80 nM
Incubation Time:

1 h
Result:

Showed no increase in apoptosis when combined with 2 Gy radiation.
Caused a significant increase in apoptosis when combined with 10 Gy radiation, compared to radiation alone.

Immunofluorescence^[2]

Cell Line:

A549 cells
Concentration:

40 nM
Incubation Time:

1 h
Result:

Combined with irradiation resulted in a statistically significant increase in the number of γH2AX foci at 8 h and 24 h compared with cells treated with irradiation alone.

Real Time qPCR^[4]

Cell Line:

HCT116, SW480, CT26, MC38
Concentration:

1 µM
Incubation Time:

2 h
Result:

Caused a sharp, time-dependent increase in mRNA levels of CXCL10, CCL5, and IFNB in HCT116 and CT26 cells, with peak expression at 8-12 hours post-irradiation.
Induced significant increases in CXCL10, CCL5, and IFNB gene expressions in SW480 and MC38 cells compared to irradiation alone.

In Vivo

Berzosertib (60 mg/kg; p.o.; daily; 10 days; 1 h before 2 Gy local tumor irradiation) hydrochloride acts synergistically with daily 2 Gy local radiation to delay subcutaneous NSCLC brain metastasis PDX tumor growth in mice^[2].
Berzosertib (60 mg/kg; p.o.; daily; 5 days; 1 h before 2.5 Gy whole brain irradiation) hydrochloride combined with daily 2.5 Gy whole brain irradiation significantly improves median overall survival and reduces intracranial tumor growth in mouse NSCLC brain metastasis xenograft model^[2].
Berzosertib (60 mg/kg; i.g.; 2 h before Gy IR, then daily for 3 days) hydrochloride produces antitumor efficacy in mouse MC38 and CT26 models, when combined with 5 Gy irradiation and anti-PD-L1^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female Hsd:athymic Nude-Foxn1 mice (6-8-week-old) subcutaneously implantated with UW-lung-16 and UW-lung-18^[2]
Dosage:

60 mg/kg
Administration:

p.o.; daily; 10 days; 1 h before 2 Gy local tumor irradiation
Result:

Delayed growth of UW-lung-16 and UW-lung-18 tumors.
Reduced estimated tumor growth curve slope for UW-lung-16 tumors significantly lower than alone, with a synergistic effect and dose enhancement factor (DEF) of 1.8.
Reduced estimated tumor growth curve slope for UW-lung-18 tumors significantly lower than alone, with a synergistic effect and DEF of 1.4.
Inhibited phospho-Chk1 (Ser345) alone and combined with irradiation.
Increased cleaved caspase-3 in the combination group.
Induced significantly more γH2AX foci in the combination group compared to other groups.

Animal Model:

Athymic nude mice intracranial implantation of luciferase-transfected UW-Lung-16 cells^[2]
Dosage:

60 mg/kg
Administration:

p.o.; daily; 5 days; 1 h before 2.5 Gy whole brain irradiation
Result:

Reduced bioluminescence total flux significantly by days 32 and 40 post-implant compared to radiation alone.
Improved median overall survival to 95 days, compared to 67 days in the radiation alone group.
Showed no significant difference in body weight between groups during or 40 days post-treatment.

Animal Model:

C57/B6J mice (female, 5-6 weeks old) subcutaneously injected with MC38 cells^[4]
Dosage:

60 mg/kg
Administration:

i.g.; 2 h before Gy IR, then daily for 3 days
Result:

Delayed tumor growth more effectively than dual or monotherapy regimens.
Led to complete tumor regression in some mice.
Extended mouse survival compared to other treatment groups.
Reduced tumor burden (as measured by bioluminescence total flux).
Decreased Ki67-positive proliferating cells.
Increased TUNEL-positive apoptotic cells.
Increased CD3⁺ and CD8⁺ tumor-infiltrating lymphocyte counts.
Elevated levels of CD11c⁺ MHC-II⁺ dendritic cells and CD11c⁺ CD8⁺ tumor-infiltrating dendritic cells.
Increased CD86 maturation marker mean fluorescence intensity.
Activated the canonical cGAS-STING-pTBK1/pIRF3 axis.
Activated the non-canonical STING-p65 axis.
Upregulated mRNA expression of innate immune-related genes Cxcl10, Ccl5, and Ifnb.

Animal Model:

Balb/C mice (female, 5-6 weeks old) subcutaneously injected with CT26 cells^[4]
Dosage:

60 mg/kg
Administration:

i.g.; 2 h before Gy IR, then daily for 3 days
Result:

Delayed tumor growth more effectively than dual or monotherapy regimens.
Extended mouse survival compared to other treatment groups.
Increased CD3⁺ and CD8⁺ tumor-infiltrating lymphocyte counts.
Elevated levels of CD11c⁺ MHC-II⁺ dendritic cells and CD11c⁺ CD8⁺ tumor-infiltrating dendritic cells.
Increased CD86 maturation marker mean fluorescence intensity.
Activated the canonical cGAS-STING-pTBK1/pIRF3 axis.
Activated the non-canonical STING-p65 axis.
Upregulated mRNA expression of innate immune-related genes Cxcl10, Ccl5, and Ifnb.
Decreased SHP1 mRNA levels and SHP1 interaction with TRAF6/STING via promoting SHP1 SUMOylation at lysine 127.

Chemical Information

CAS No. 1428935-04-9
Appearance Solid
Molecular Weight 500.01
Formula C₂₄H₂₆ClN₅O₃S
Color Light yellow to yellow
SMILES

NC1=NC=C(C2=CC=C(S(=O)(C(C)C)=O)C=C2)N=C1C3=CC(C4=CC=C(CNC)C=C4)=NO3.Cl
Synonyms

VE-822 hydrochloride; VX-970 hydrochloride; M6620 hydrochloride
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Publications (26)

All In Vivo Efficacy StudyFlow CytometryCell Proliferation/Viability AssayIFWB

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Journal Impact Factor

Cancer Commun (Lond)

Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer. [Abstract]

2023 Apr;43(4):435-454. PMID: 36855844

Berzosertib hydrochloride purchased from MedChemExpress. Usage Cited in: Cancer Commun (Lond). 2023 Apr;43(4):435-454. [Abstract]

Berzosertib (60 mg/kg) was administered by gavage 2 h before IR and consecutively for the next three days. Representative IHC images of CD3 staining of MC38 tumors were shown.

Berzosertib hydrochloride purchased from MedChemExpress. Usage Cited in: Cancer Commun (Lond). 2023 Apr;43(4):435-454. [Abstract]

Berzosertib (60 mg/kg) was administered by gavage 2 h before IR and consecutively for the next three days. Representative flow cytometry images and quantitative analysis of TILs in CT26 tumors were obtained.

Berzosertib hydrochloride purchased from MedChemExpress. Usage Cited in: Cancer Commun (Lond). 2023 Apr;43(4):435-454. [Abstract]

Berzosertib (0–2 μM; 24 h). Cell viability assay of multiple CRC cell lines treated with ATRi and IR + ATRi was performed.

Berzosertib hydrochloride purchased from MedChemExpress. Usage Cited in: Cancer Commun (Lond). 2023 Apr;43(4):435-454. [Abstract]

Berzosertib (1 μM). Cell cycle distribution analysis of HCT116 and CT26 cells treated with IR and IR + ATRi. Representative flow cytometry images of phospho-histone H3+ cells in HCT116 and CT26 cells were shown.

Berzosertib hydrochloride purchased from MedChemExpress. Usage Cited in: Cancer Commun (Lond). 2023 Apr;43(4):435-454. [Abstract]

Berzosertib (1 μM; 14 h). IF images of dsDNA and cGAS staining in HCT116 cells were shown.

Berzosertib hydrochloride purchased from MedChemExpress. Usage Cited in: Cancer Commun (Lond). 2023 Apr;43(4):435-454. [Abstract]

Berzosertib (1 μM; 14 h) was used. Immunoblotting of the key proteins from the canonical cGAS-STING axis in multiple CRC cell lines was performed.
Nat Commun

Myc targeted CDK18 promotes ATR and homologous recombination to mediate PARP inhibitor resistance in glioblastoma. [Abstract]

2019 Jul 2;10(1):2910. PMID: 31266951
Sci Transl Med

BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers. [Abstract]

2020 Feb 19;12(531):eaax2625. PMID: 32075943
Clin Cancer Res

Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression. [Abstract]

2022 Jun 1;28(11):2397-2408. PMID: 35325095
Cancer Lett

2026 Feb 4;642:218300.
Cancer Lett

Targeting ATR signaling in sarcoma with homologous recombination deficiency. [Abstract]

2026 Apr 1:642:218300. PMID: 41651400
Cell Death Dis

KDM1A epigenetically enhances RAD51 expression to suppress the STING-associated anti-tumor immunity in esophageal squamous cell carcinoma. [Abstract]

2024 Dec 6;15(12):882. PMID: 39638799
Cell Syst

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations. [Abstract]

2018 Apr 25;6(4):424-443.e7. PMID: 29655704
NPJ Breast Cancer

CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen. [Abstract]

2025 Dec 3;11(1):135. PMID: 41339342
Biomed Pharmacother

Dihydroartemisinin enhances NKG2D CAR-T cell therapy against solid tumors by inducing NKG2D ligands and remodeling the tumor microenvironment. [Abstract]

2026 Feb:195:118974. PMID: 41529511
Cell Rep

MMB-FOXM1-driven premature mitosis is required for CHK1 inhibitor sensitivity. [Abstract]

2021 Mar 2;34(9):108808. PMID: 33657372
Oncogenesis

STAG2 expression imparts distinct therapeutic vulnerabilities in muscle-invasive bladder cancer cells. [Abstract]

2025 Mar 1;14(1):4. PMID: 40025053
Eur J Med Chem

New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs. [Abstract]

2017 Feb 15:127:691-702. PMID: 27823879

Berzosertib hydrochloride 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.
Cancer Immunol Immunother

Combination of ataxia telangiectasia and Rad3-related inhibition with ablative radiotherapy remodels the tumor microenvironment and enhances immunotherapy response in lung cancer. [Abstract]

2024 Nov 2;74(1):8. PMID: 39487895
Cell Oncol (Dordr)

Novel preclinical gastroenteropancreatic neuroendocrine neoplasia models demonstrate the feasibility of mutation-based targeted therapy. [Abstract]

2022 Dec;45(6):1401-1419. PMID: 36269546
Mol Cancer Res

Inhibition of the ATR-CHK1 Pathway in Ewing Sarcoma Cells Causes DNA Damage and Apoptosis via the CDK2-Mediated Degradation of RRM2. [Abstract]

2020 Jan;18(1):91-104. PMID: 31649026
Mol Oncol

Olaparib synergy screen reveals Exemestane induces replication stress in triple-negative breast cancer. [Abstract]

2025 Jul 13. PMID: 40652528
J Mol Med (Berl)

Combination of PARP inhibitor and temozolomide to suppress chordoma progression. [Abstract]

2019 Aug;97(8):1183-1193. PMID: 31201471
J Biol Chem

The E3 ligase β-TRCP1 earmarks OTUD3 for destruction to fine-tune cGAS activation. [Abstract]

2026 Jun;302(6):111461. PMID: 41999888
Bioengineering (Basel)

Precision Oncology for High-Grade Gliomas: A Tumor Organoid Model for Adjuvant Treatment Selection. [Abstract]

2025 Oct 19;12(10):1121. PMID: 41155119
Anticancer Res

Schlafen11 Expression Is Associated With the Antitumor Activity of Trabectedin in Human Sarcoma Cell Lines. [Abstract]

2019 Jul;39(7):3553-3563. PMID: 31262879
Patent

US20240285616A1
Research Square Preprint

2024 Nov 06.
Patent

US20240285616A1.
bioRxiv

2024 Mar 28.
University of London

2021 Sep.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (288 KB)
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)
- Portuguese - PT (252 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Schnoell J, et al. The ATR inhibitor berzosertib acts as a radio- and chemosensitizer in head and neck squamous cell carcinoma cell lines. Invest New Drugs. 2023;41(6):842-850. [Content Brief]

[2]. Baschnagel AM, et al. ATR Inhibitor M6620 (VX-970) Enhances the Effect of Radiation in Non-Small Cell Lung Cancer Brain Metastasis Patient-Derived Xenografts. Mol Cancer Ther. 2021;20(11):2129-2139. [Content Brief]

[3]. 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;3(12):e441. Published 2012 Dec 6. [Content Brief]

[4]. Liu C, et al. Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer. Cancer Commun (Lond). 2023;43(4):435-454. [Content Brief]

[5]. Gorainow N, et al. Berzosertib enhances the sensitivity of pediatric diffuse midline glioma H3K27-altered cells to radiotherapy. Cell Death Dis. 2026;17(1):331. Published 2026 Mar 20. [Content Brief]

[6]. Kurmasheva RT, et al. Initial testing (stage 1) of M6620 (formerly VX-970), a novel ATR inhibitor, alone and combined with cisplatin and melphalan, by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2018;65(2):10.1002/pbc.26825. [Content Brief]

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Berzosertib hydrochloride

26 Cited Publications

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Berzosertib hydrochloride

Apoptosis Compound Library

Cell Cycle/DNA Damage Compound Library

Immunology/Inflammation Compound Library

Kinase Inhibitor Library

PI3K/Akt/mTOR Compound Library

Anti-Cancer Compound Library

CNS-Penetrant Compound Library

Small Molecule Immuno-Oncology Compound Library

Anti-Aging Compound Library

Oxygen Sensing Compound Library

Glycolysis Compound Library

Pyroptosis Compound Library

Cytoskeleton Compound Library

Orally Active Compound Library

Anti-Lung Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Anti-Obesity Compound Library

Glucose Metabolism Compound Library

Anti-Colorectal Cancer Compound Library

Cancer Stem Cells Compound Library

Highly Selective Inhibitors Library

Highly Selective Activators Library

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Serine/Threonine Kinase Inhibitor Library

Immunopotentiator Compound Library

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Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

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Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

High-Efficiency Gene Editing Compound Library

Publications Citing Use of MedChemExpress (MCE) Berzosertib hydrochloride

All ATM/ATR Isoforms

All Caspase Isoforms

Biological Activity

Chemical Information

Publications (26)

Purity & Documentation

References

Calculators

Help & FAQs

Berzosertib hydrochloride Related Classifications

Cat. No.: HY-13902A