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Chemical Structure| 1232416-25-9 Chemical Structure| 1232416-25-9

Structure of Berzosertib
CAS No.: 1232416-25-9

Chemical Structure| 1232416-25-9

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Berzosertib (VE-822) inhibits ATR with a Ki value of less than 0.2 nM and also inhibits ATM with a Ki of 34 nM.

Synonyms: VE-822; VX970; M6620

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Product Details of Berzosertib

CAS No. :1232416-25-9
Formula : C24H25N5O3S
M.W : 463.55
SMILES Code : NC1=NC=C(C2=CC=C(S(=O)(C(C)C)=O)C=C2)N=C1C3=CC(C4=CC=C(CNC)C=C4)=NO3
Synonyms :
VE-822; VX970; M6620
MDL No. :MFCD27976794
InChI Key :JZCWLJDSIRUGIN-UHFFFAOYSA-N
Pubchem ID :59472121

Safety of Berzosertib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of Berzosertib

DNA
PI3K-AKT

Isoform Comparison

Biological Activity

Target
  • ATR

    ATR, IC50:19 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
human gastric cancer organoids 10 μM 48 h To test the effect of Berzosertib on the viability of ARID1A wild-type and mutant human gastric cancer organoids, results showed that Berzosertib selectively reduced the viability of ARID1A mutant organoids. Sci Adv. 2024 Mar 15;10(11):eadh4435.
DMS 114 1 µM 6 or 24 h Berzosertib specifically inhibited the activation of ATR and its downstream target CHK1, with less notable effects on other DNA damage repair pathways, leading to continued cell cycle progression and ultimately mitotic catastrophe and cell death. EMBO Mol Med. 2023 Aug 7;15(8):e17313.
A549 cells 1 µM 72 h Pre-treatment with Berzosertib significantly increased the radiosensitivity of A549 cells, reducing the radioresistance of shScr cells to the level of shSTX18 cells. Cell Death Dis. 2022 Jun 6;13(6):529.
H460 cells 1 µM 72 h Pre-treatment with Berzosertib significantly increased the radiosensitivity of H460 cells, and H460 cells were intrinsically more sensitive to Berzosertib. Cell Death Dis. 2022 Jun 6;13(6):529.
PDOVCs#3 cells 80 nM 1 h Berzosertib in combination with CDDP significantly increased DNA damage in PDOVCs#3 and PDOVCs#4, reversing DDUP-mediated DNA damage repair. Cell Death Dis. 2023 Aug 26;14(8):568.
PDOVCs#4 cells 80 nM 1 h Berzosertib in combination with CDDP significantly increased DNA damage in PDOVCs#3 and PDOVCs#4, reversing DDUP-mediated DNA damage repair. Cell Death Dis. 2023 Aug 26;14(8):568.
Huh7 cells 5 μM 48 h To evaluate the cytotoxic and DNA damage effects of Berzosertib on Huh7 cells Hepatology. 2023 Nov 1;78(5):1462-1477.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice LMS33 PDX model Oral 60 mg/kg 5 days per week for 21 days To evaluate the antitumor activity of the ATR inhibitor Berzosertib in the LMS33 PDX model. Results showed that tumor growth was not significantly decreased over the 21-day treatment period, indicating the lack of activity of this drug as monotherapy in this model. Clin Cancer Res. 2022 Jun 1;28(11):2397-2408
Mice PDX-06 Intravenous (lurbinectedin), Intraperitoneal (berzosertib) 20 mg/kg Every 7 days for 4 cycles In the PDX-06 model, lurbinectedin alone almost completely inhibited tumor growth, and the addition of berzosertib did not significantly improve efficacy. However, berzosertib cotreatment significantly reduced p-CHK1 activation, indicating target engagement. EMBO Mol Med. 2023 Aug 7;15(8):e17313.
Mouse PDX-06 Intravenous and intraperitoneal 20 mg/kg Every 7 days for 4 cycles Assess the in vivo synergy of Berzosertib with Lurbinectedin EMBO Mol Med. 2023 Aug 7;15(8):e17313.
NOD-SCID IL-2rγ−/− (NSG) mice Ovarian cancer xenograft model Intraperitoneal injection 60 mg/kg Three times per week for 6 weeks Berzosertib significantly reversed DDUP-mediated carboplatin resistance, reducing tumor volume and increasing tumor cell apoptosis. Cell Death Dis. 2023 Aug 26;14(8):568.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT03309150 Advanced Stage Solid Tumors PHASE1 COMPLETED 2024-01-26 Royal Marsden NHS Foundation T... More >>rust, Sutton, United Kingdom Less <<
NCT03718091 Solid Tumor|Leiomyosarcoma|Ost... More >>eosarcoma Less << PHASE2 COMPLETED 2020-07-08 Massachusetts General Hospital... More >> Cancer Center, Boston, Massachusetts, 02214, United States|Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States|Boston Children Hospital, Boston, Massachusetts, 02215, United States|Dana Farber Cancer Institute, Boston, Massachusetts, 02215, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.79mL

2.16mL

1.08mL

21.57mL

4.31mL

2.16mL

References

 

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