Biological Activity

Bioactivity / Mechanism

VE-822 inhibits ATR in biochemical kinase profiling: the reported Ki was <0.0002 μM for ATR, compared with 0.034 μM for ATM and >4 μM for DNA-PK. These assay endpoints describe the tested compound and do not validate a current commercial lot. [1]

In H2009 lung cancer cells, VX-970 (VE-822) suppressed cisplatin-induced Chk1 Ser345 phosphorylation and increased damage-associated H2AX and KAP1 phosphorylation after 17 h. Single-agent and combination controls support this cellular ATR-pathway effect. [2]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target	Activity	Value
ATR (HT29 cells)		19 nM
ATM (HT29 cells)		34 μM

In Vitro Studies

In CT26 cells, berzosertib reduced CellTiter-Glo viability with IC50 values of 3.05 μM at 24 h and 1.98 μM at 48 h. These cellular viability values should be distinguished from biochemical ATR inhibition potency. [3]

Biochemical kinase selectivity of VE-822

Biochemical assay · ATR, ATM and DNA-PK biochemical kinase assays [1]

VE-822 showed lower reported Ki for ATR than for ATM or DNA-PK in the original kinase panel.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
ATR biochemical inhibition	Ki <0.0002 μM	[1]
ATM biochemical inhibition	Ki 0.034 μM	[1]
DNA-PK biochemical inhibition	Ki >4 μM	[1]

Literature-Reported Treatment Conditions

Method: Biochemical kinase profiling.
Reported limits: Concentration series, incubation time, replicate count and detailed assay controls are not given in Table 1; the Methods refer to earlier procedures, which were not retrieved. No ATP-competitive binding-mode or precision/replication claim is adopted.

Methods and source locations

Compound reported in the paper: Berzosertib (VE-822); Compound label in the paper: VE-822

Compound-level evidence for the named material; no salt conversion, stereochemical extrapolation or current Adooq lot validation.

Table 1, biochemical Ki columns; Materials and Methods, Biochemical and cellular inhibition of ATR and related kinases; ATR inhibitor preparation and treatment

ATR biochemical inhibition: Biochemical kinase inhibition; assay procedures referenced by the paper to Reaper et al. (2011). — Table 1, biochemical Ki columns; Materials and Methods, Biochemical and cellular inhibition of ATR and related kinases; ATR inhibitor preparation and treatment

ATM biochemical inhibition: Same reported biochemical profiling panel. — Table 1, biochemical Ki columns; Materials and Methods, Biochemical and cellular inhibition of ATR and related kinases; ATR inhibitor preparation and treatment

DNA-PK biochemical inhibition: Same reported biochemical profiling panel. — Table 1, biochemical Ki columns; Materials and Methods, Biochemical and cellular inhibition of ATR and related kinases; ATR inhibitor preparation and treatment

Berzosertib concentration response in CT26 cells

Cell-based study · Murine CT26 colorectal carcinoma cells (ATCC CRL-2638). [3]

Berzosertib reduced ATP-dependent viability over micromolar concentration ranges. The 48 h IC50 was lower than the 24 h value; these are cellular viability endpoints, not biochemical ATR IC50 values.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
CellTiter-Glo viability after 24 h berzosertib	IC50 3.05 μM (95% CI: 2.09–4.40 μM)	[3]
CellTiter-Glo viability after 48 h berzosertib	IC50 1.98 μM (95% CI: 1.45–2.72 μM)	[3]

Literature-Reported Treatment Conditions

Treatment concentration: 0.15, 0.5, 1.5, 5, 15 and 50 μM berzosertib.
Exposure duration: 24 or 48 h.
Method: CellTiter-Glo 2.0 ATP-luminescence assay; normalization to untreated/DMSO controls and complete-medium background.
Vehicle: DMSO stock; untreated cells described as DMSO controls.
Reported limits: Final DMSO percentage not specified in the read Methods. No radiation or other agent in the selected berzosertib concentration-response groups.

Methods and source locations

Compound reported in the paper: Berzosertib (VE-822); Compound label in the paper: berzosertib

Compound-level evidence for the named material; no salt conversion, stereochemical extrapolation or current Adooq lot validation.

Sections 2.1, 2.6, 2.7 and 3.4; Figure 4A–C and caption

CellTiter-Glo viability after 24 h berzosertib: Sigmoidal nonlinear regression; mean of three independent replicated experiments; triplicate treated and untreated wells. Figure curves/bars show mean±SEM. — Sections 2.1, 2.6, 2.7 and 3.4; Figure 4A–C and caption

CellTiter-Glo viability after 48 h berzosertib: Same concentration-response design and normalization; duration groups retained in one study. — Sections 2.1, 2.6, 2.7 and 3.4; Figure 4A–C and caption

VX-970 inhibition of cisplatin-induced ATR signaling in H2009 cells

Cell-based study · Human H2009 lung cancer cells; original paper reports ATCC origin and no additional in-house authentication. [2]

VX-970 suppressed cisplatin-induced Chk1 Ser345 phosphorylation in a concentration-dependent manner while increasing H2AX Ser139 and KAP1 Ser824 phosphorylation. The blots support ATR-pathway inhibition and accumulation of damage-associated signaling under these conditions.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Chk1 Ser345 phosphorylation after 17 h	Qualitative immunoblot response Concentration-dependent suppression with VX-970 plus cisplatin relative to cisplatin alone.	[2]
H2AX Ser139 and KAP1 Ser824 phosphorylation	Qualitative immunoblot response Marked increases with co-treatment; mild induction with VX-970 alone.	[2]

Literature-Reported Treatment Conditions

Treatment concentration: VX-970: 0, 0.006, 0.025, 0.1, 0.4 and 1.6 μM in each series.
Exposure duration: 17 h (overnight).
Method: Immunoblot analysis of exponentially growing H2009 cells.
Co-treatment: 20 μM cisplatin in the combination series; corresponding no-cisplatin series included.
Reported limits: Vehicle concentration and replicate number are not specified in the selected Figure 1 experiment; quantitative effect sizes and statistical significance are not claimed.

Methods and source locations

Compound reported in the paper: Berzosertib (VE-822; VX-970); Compound label in the paper: VX-970

Compound-level ATR-pathway pharmacology in H2009 cells; no clinical or current-lot conclusion.

Figure 1A–B and caption; Results, VX-970 inhibits cisplatin-induced phosphorylation of Chk1 and increases levels of DNA damage markers in vitro; Methods, Cell Lines and Immunoblotting Analysis

Chk1 Ser345 phosphorylation after 17 h: Immunoblot with total Chk1, total H2AX, total KAP1 and GAPDH controls; both VX-970-alone and cisplatin-combination concentration series. — Figure 1A–B and caption; Results, VX-970 inhibits cisplatin-induced phosphorylation of Chk1 and increases levels of DNA damage markers in vitro; Methods, Cell Lines and Immunoblotting Analysis

H2AX Ser139 and KAP1 Ser824 phosphorylation: Same 17 h immunoblot experiment; no densitometry or exact fold change inferred. — Figure 1A–B and caption; Results, VX-970 inhibits cisplatin-induced phosphorylation of Chk1 and increases levels of DNA damage markers in vitro; Methods, Cell Lines and Immunoblotting Analysis

In Vivo Studies

In PSN-1 pancreatic tumor xenografts, oral VE-822 (60 mg/kg) combined with a single 6 Gy radiation dose more than doubled the time to 600 mm³ tumor volume versus radiation alone. VE-822 monotherapy did not delay tumor growth at this dose. [1]

In an acute BALB/c mouse study, a single intravenous berzosertib dose (60 mg/kg) before 6 Gy total-body irradiation partially attenuated WBC and lymphocyte loss at 48 h. Berzosertib alone increased neutrophils. These blood-count observations do not establish repeated-dose or human safety. [3]

VE-822 plus single-fraction radiation in PSN-1 xenografts

Animal study · Female BALB/c nude mice bearing subcutaneous PSN-1 pancreatic tumor xenografts; n=4–5 per group; treatment began near 80 mm³ tumor volume. [1]

Combining VE-822 with radiation prolonged time to 600 mm³ relative to radiation alone; VE-822 monotherapy did not delay tumor growth.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Time from treatment day 0 to tumor volume 600 mm³	TV600 comparison Both 4-day and 6-day VE-822 + XRT schedules more than doubled TV600 versus XRT alone (P<0.001); 6-day combination exceeded 4-day combination (P<0.001).	[1]
Tumor growth with VE-822 alone versus vehicle	Qualitative comparison No tumor growth effect at the tested dose.	[1]

Conditions shared by the study groups

Route: Oral gavage for VE-822 or vehicle; external irradiation for XRT.
Frequency: Once daily VE-822 where given; single XRT fraction where given.
Vehicle: 10% Vitamin E d-alpha tocopheryl polyethylene glycol 1000 succinate; 200 μL gavage.

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Vehicle control Vehicle only	Baseline comparator.	Baseline tumor growth.	[1]
VE-822 alone 60 mg/kg VE-822	Vehicle.	No tumor-growth delay at this dose.	[1]
XRT alone 6 Gy XRT	Vehicle and VE-822 alone.	Longer TV600 than either control (P<0.001).	[1]
Four-day VE-822 plus XRT 60 mg/kg VE-822 + 6 Gy XRT	XRT alone.	More than doubled TV600 versus XRT alone (P<0.001).	[1]
Six-day VE-822 plus XRT 60 mg/kg VE-822 + 6 Gy XRT	XRT alone and four-day combination.	More than doubled TV600 versus XRT alone; longer than four-day combination (both P<0.001).	[1]

Vehicle control: Model: Female BALB/c nude mice bearing subcutaneous PSN-1 pancreatic tumor xenografts; n=4–5 per group; treatment began near 80 mm³ tumor volume.; Treatment course: Matched control schedule.; Reported limits: Exact TV600 values not extracted from graph.

VE-822 alone: Model: Female BALB/c nude mice bearing subcutaneous PSN-1 pancreatic tumor xenografts; n=4–5 per group; treatment began near 80 mm³ tumor volume.; Treatment course: Days 0–5.; Reported limits: Exact TV600 values not extracted from graph.

XRT alone: Model: Female BALB/c nude mice bearing subcutaneous PSN-1 pancreatic tumor xenografts; n=4–5 per group; treatment began near 80 mm³ tumor volume.; Treatment course: Day 1.; Reported limits: Exact TV600 values not extracted from graph.

Four-day VE-822 plus XRT: Model: Female BALB/c nude mice bearing subcutaneous PSN-1 pancreatic tumor xenografts; n=4–5 per group; treatment began near 80 mm³ tumor volume.; Treatment course: VE-822 days 0–3; XRT day 1.; Reported limits: Exact TV600 values not extracted from graph.

Six-day VE-822 plus XRT: Model: Female BALB/c nude mice bearing subcutaneous PSN-1 pancreatic tumor xenografts; n=4–5 per group; treatment began near 80 mm³ tumor volume.; Treatment course: VE-822 days 0–5; XRT day 1.; Reported limits: Exact TV600 values not extracted from graph.

Methods and source locations

Compound reported in the paper: Berzosertib (VE-822); Compound label in the paper: VE-822

Compound-level evidence for the named material; no salt conversion, stereochemical extrapolation or current Adooq lot validation.

Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

Time from treatment day 0 to tumor volume 600 mm³: Tumor growth delay; original group curves and means±S.D.; n=4–5. No exact days estimated from bars. — Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

Tumor growth with VE-822 alone versus vehicle: Same growth-delay experiment I, including vehicle and single-agent controls. — Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

Vehicle control · Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

VE-822 alone · Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

XRT alone · Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

Four-day VE-822 plus XRT · Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

Six-day VE-822 plus XRT · Figure 4b–c, growth delay experiment I and caption; Results, Efficacy of VE-822 combined with radiotherapy in xenografts; Materials and Methods, ATR inhibitor preparation and treatment, Xenograft studies, Statistical analyses

Acute blood-count responses to berzosertib with total-body irradiation

Animal study · Female BALB/c mice, 5–7 weeks at purchase; four berzosertib-cohort groups, N=5/group. [3]

At 48 h, berzosertib plus TBI had higher WBC and lymphocyte counts than TBI alone, while counts remained below vehicle controls. Berzosertib alone increased neutrophils. This is an acute blood-count study, not evidence of general radioprotection or long-term safety.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Absolute white blood cell counts at 48 h: TBI alone versus berzosertib + TBI	Blood count 1.44 vs 2.19 × 10^9/L; author-reported significant amelioration of loss.	[3]
Absolute lymphocyte counts at 48 h: TBI alone versus berzosertib + TBI	Blood count 0.288 vs 0.986 × 10^9/L; author-reported significant amelioration of loss.	[3]
Neutrophil response to berzosertib monotherapy	Qualitative observation Increased neutrophils after berzosertib alone; combination largely resembled TBI alone.	[3]

Conditions shared by the study groups

Frequency: Single administration/exposure.
Treatment course: Day 0 treatment; evaluation 48 h after TBI.

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Vehicle control Vehicle only	Baseline comparator.	Higher WBC and lymphocyte counts than TBI-exposed groups (Figure 1C).	[3]
Berzosertib alone 60 mg/kg	Vehicle.	Increased neutrophils observed; no statistical comparison with vehicle asserted.	[3]
TBI alone 6 Gy	Vehicle.	Reduced WBC and lymphocyte counts.	[3]
Berzosertib plus TBI 60 mg/kg berzosertib + 6 Gy TBI	TBI alone.	Higher WBC and lymphocyte counts at 48 h; not restoration to baseline.	[3]

Vehicle control: Model: Female BALB/c mice, 5–7 weeks at purchase; four berzosertib-cohort groups, N=5/group.; Route: Matched vehicle route not independently specified in read text.; Reported limits: Vehicle formulation referred to an earlier paper, not retrieved.

Berzosertib alone: Model: Female BALB/c mice, 5–7 weeks at purchase; four berzosertib-cohort groups, N=5/group.; Route: Intravenous.; Reported limits: Vehicle formulation referred to an earlier paper, not retrieved.

TBI alone: Model: Female BALB/c mice, 5–7 weeks at purchase; four berzosertib-cohort groups, N=5/group.; Route: External total-body irradiation.; Reported limits: Vehicle formulation referred to an earlier paper, not retrieved.

Berzosertib plus TBI: Model: Female BALB/c mice, 5–7 weeks at purchase; four berzosertib-cohort groups, N=5/group.; Route: Intravenous drug; external total-body irradiation.; Reported limits: Vehicle formulation referred to an earlier paper, not retrieved.

Methods and source locations

Compound reported in the paper: Berzosertib (VE-822); Compound label in the paper: berzosertib

Compound-level evidence for the named material; no salt conversion, stereochemical extrapolation or current Adooq lot validation.

Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

Absolute white blood cell counts at 48 h: TBI alone versus berzosertib + TBI: VETSCAN HM5 blood counts; Figure 1 bold lines are geometric means. Mann–Whitney comparisons uncorrected for multiple testing; N=5/group. — Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

Absolute lymphocyte counts at 48 h: TBI alone versus berzosertib + TBI: Same CBC design; exact values from section 3.2; figure confirms direction without digitizing individual points. — Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

Neutrophil response to berzosertib monotherapy: Same CBC cohort; no monotherapy significance claim is made here, since section 3.2 reports direction without a monotherapy P-value. — Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

Vehicle control · Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

Berzosertib alone · Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

TBI alone · Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

Berzosertib plus TBI · Sections 2.1–2.4, 2.6 and 3.2; Figure 1C/F and caption; Discussion, single-dose and species limitations

Specifications

Manufacturer	Adooq Bioscience
Actions	Inhibitor
CAS Number	1232416-25-9
Applications	ATR inhibitor
Formula	C₂₄H₂₅N₅O₃S
Molecular Weight	463.55
Synonyms	VE822
SMILES	CC(C)S(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C3=CC(=NO3)C4=CC=C(C=C4)CNC)N

Storage & Solubility

In Vitro Solubility

Reported Solubility

Solvent	Reported Solubility
DMSO	36 mg/mL (77.66 mM)
Water	Insoluble
Ethanol	Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration: 10 mg/mL
Vehicle: 5% DMSO+45% PEG 300+H2O

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] Fokas E, Prevo R, Pollard JR, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation Cell death & disease (2012). PMID: 23222511 DOI: 10.1038/cddis.2012.181 Source material
[2] Hall AB, Newsome D, Wang Y, et al. Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970 Oncotarget (2014). PMID: 25010037 DOI: 10.18632/oncotarget.2158 Source material
[3] Deppas JJ, Kiesel BF, Guo J, et al. Comparative in vivo toxicology of ATR inhibitors ceralasertib, elimusertib, and berzosertib alone and in combination with ionizing radiation Toxicology and applied pharmacology (2025). PMID: 40339611 DOI: 10.1016/j.taap.2025.117375 Source material

Publications

1 publication citing this product

Joshua J Deppas, .et al. , Toxicol Appl Pharmacol, 2025, Jul:500:117375 PMID: 40339611

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Berzosertib (VE-822)

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Berzosertib 1 mg

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Biological Activity

Bioactivity / Mechanism

Target & Activity

In Vitro Studies

Biochemical kinase selectivity of VE-822

Literature-Reported Treatment Conditions

Berzosertib concentration response in CT26 cells

Literature-Reported Treatment Conditions

VX-970 inhibition of cisplatin-induced ATR signaling in H2009 cells

Literature-Reported Treatment Conditions

In Vivo Studies

VE-822 plus single-fraction radiation in PSN-1 xenografts

Conditions shared by the study groups

Acute blood-count responses to berzosertib with total-body irradiation

Conditions shared by the study groups

Specifications

Storage & Solubility

In Vitro Solubility

Reported Solubility

Preparing Stock Solutions

In Vivo Preparation

Storage

Research References

Publications

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