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

Cat. No.: HY-13902A: Data Sheet Handling Instructions
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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.

CAS No. : 1428935-04-9

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24 Publications Citing Use of MCE Berzosertib hydrochloride

In Vivo Efficacy Study

Flow Cytometry

Cell Proliferation/Viability Assay

: 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.

: 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.

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Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]

Caspase-3

ATR

0.2 nM (Ki)

ATM

34 nM (Ki)

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.

Molecular Weight

500.01

Formula

C₂₄H₂₆ClN₅O₃S

CAS No.

1428935-04-9

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

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.

Berzosertib hydrochloride Related Classifications

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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.

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