| Field | Specification |
|---|---|
| Target | |
| Alternative names | VE-822; VX-970; M6620 |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C24H25N5O3S |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
Berzosertib, also known as VE-822, VX-970, or M6620, is an orally active, CNS-penetrant, selective inhibitor of ATR kinase. It blocks ATR kinase activity, abrogates the G2/M cell cycle checkpoint, and impairs DNA damage repair. In cancer cells, it induces apoptosis, inhibits colony migration and cell proliferation, and activates the cGAS-STING axis. Berzosertib can be used to research cancers such as head and neck squamous cell carcinoma and colorectal cancer[1][2][3][4][5][6]. It is supplied as a light yellow to yellow solid (C24H25N5O3S, MW 463.55) at 99.44% purity.
Physical & Chemical Properties
| CAS Number | 1232416-25-9 |
|---|---|
| Molecular Formula | C24H25N5O3S |
| Molecular Weight | 463.55 g/mol |
| Purity | 99.44% |
| Appearance | Solid |
| 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 |
| Target | ATR, ATM, Caspase-3 |
| Signaling Pathway | Cell Cycle/DNA Damage; PI3K/Akt/mTOR; Apoptosis; Immunology/Inflammation |
| Solubility | In Vitro: DMSO: 16.67 mg/mL (35.96 mM; Requires sonication and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 6 months; -20°C, 1 month. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target[1]
|
ATR 0.2 nM (Ki) |
ATM 34 nM (Ki) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 16.67 mg/mL (35.96 mM) | requires sonication and warming and heat to 60°C; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 1.67 mg/mL (3.60 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 1.67 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (16.7 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Data provided by the manufacturer.
In Vitro
In Cal-27 and FaDu HNSCC cell lines, Berzosertib (0.031-1 μM; 72 h) lowers cell viability, yielding IC50 values of 0.285 μM (Cal-27) and 0.252 μM (FaDu)[1]. Berzosertib (0.125-0.5 μM; 24-48 h) suppresses migration of Cal-27 and FaDu HNSCC cells[1]. Berzosertib (0.25-0.5 μM; 48 h) triggers apoptosis in both Cal-27 and FaDu cells[1]. Berzosertib (48-72 h) suppresses proliferation of A549, NCI-H226, and NCI-H520 cells, with IC50 values in the 1-4 μM range[2]. In A549, NCI-H226, and NCI-H520 NSCLC cell lines, Berzosertib (40-80 nM; 1 h) increases radiosensitivity[2]. In the same NSCLC cell lines, Berzosertib (40 nM; 1 h) blocks radiation-induced ATR (Thr1989) phosphorylation without affecting ATM (Ser1981) activation[2]. In A549 NSCLC cells, Berzosertib (40 nM; 1 h) removes the radiation-induced G2/M cell cycle checkpoint and shifts cells into G1 phase[2]. Combined with 10 Gy irradiation, but not 2 Gy, Berzosertib (40-80 nM; 1 h) increases radiation-induced apoptosis in A549 NSCLC cells[2]. Berzosertib (40 nM; 1 h) impairs DNA double-strand break repair in A549 cells[2]. In HCT116 and CT26 cells, Berzosertib (1 μM; 2 h) weakens initiation and maintenance of the irradiation-induced G2/M checkpoint, promoting mitotic entry after DNA damage[4]. In HCT116 and CT26 colorectal cancer cell lines, Berzosertib (1 μM; 2 h) combined with 5 Gy irradiation raises micronuclei formation and cytosolic dsDNA levels[4]. Berzosertib (1 μM; 2 h) plus 5 Gy irradiation strongly activates the canonical cGAS-STING-pTBK1/pIRF3 pathway in HCT116, SW480, CT26, and MC38 cells and upregulates expression of the interferon-stimulated genes CXCL10, CCL5, and IFNB[4]. In HCT116 cells, Berzosertib (1 μM; 2 h) with 5 Gy irradiation prevents SHP1 recruitment to the TRAF6/STING complex, strengthening the TRAF6-STING interaction[4].
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. |
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. |
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 (p.o.; 60 mg/kg; daily for 10 days; dosed 1 h before 2 Gy local tumor irradiation) delays the growth of subcutaneous NSCLC brain metastasis PDX tumors in mice, acting synergistically with daily 2 Gy local radiation[2]. In a mouse NSCLC brain metastasis xenograft model, median overall survival is significantly improved and intracranial tumor growth is reduced by Berzosertib (p.o.; 60 mg/kg; daily for 5 days; dosed 1 h before 2.5 Gy whole brain irradiation) when it is combined with daily 2.5 Gy whole brain irradiation[2]. In mouse MC38 and CT26 models, antitumor efficacy is produced by Berzosertib (i.g.; 60 mg/kg; 2 h before Gy IR, then daily for 3 days) when it is combined with 5 Gy irradiation and anti-PD-L1[4].
| 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 | 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. |
| 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 | 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. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer. Cancer Commun (Lond) 2023 Apr;43(4):435-454. PMID: 36855844
Myc targeted CDK18 promotes ATR and homologous recombination to mediate PARP inhibitor resistance in glioblastoma. Nat Commun 2019 Jul 2;10(1):2910.
BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers. Sci Transl Med 2020 Feb 19;12(531):eaax2625.
KDM1A epigenetically enhances RAD51 expression to suppress the STING-associated anti-tumor immunity in esophageal squamous cell carcinoma. Cell Death Dis 2024 Dec 6;15(12):882. PMID: 39638799
Cancer Lett. 2026 Feb 4;642:218300.
Targeting ATR signaling in sarcoma with homologous recombination deficiency. Cancer Lett 2026 Apr 1:642:218300. PMID: 41651400
Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression. Clin Cancer Res 2022 Jun 1;28(11):2397-2408. PMID: 35325095
CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen. NPJ Breast Cancer 2025 Dec 3;11(1):135. PMID: 41339342
MMB-FOXM1-driven premature mitosis is required for CHK1 inhibitor sensitivity. Cell Rep 2021 Mar 2;34(9):108808. PMID: 33657372
A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations. Cell Syst 2018 Apr 25;6(4):424-443.e7.
