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Berzosertib(VE-822 VX-970)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Berzosertib(VE-822 VX-970)图片
CAS NO:1232416-25-9
规格:≥98%

产品介绍
理化性质和储存条件
Molecular Weight (MW)463.55
FormulaC24H25N5O3S
CAS No.1232416-25-9
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 36 mg/mL (77.66 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other info

Chemical Name: 5-(4-(isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine.

InChi Key: JZCWLJDSIRUGIN-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H25N5O3S/c1-15(2)33(30,31)19-10-8-18(9-11-19)21-14-27-24(25)23(28-21)22-12-20(29-32-22)17-6-4-16(5-7-17)13-26-3/h4-12,14-15,26H,13H2,1-3H3,(H2,25,27)

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

VE822; VE-822; VE 822; M6620; M-6620; M 6620; VX970; VX-970; VX 970

实验参考方法
In Vitro

In vitro activity: VE-822 (80 nM) attenuates ATR signaling pathway and reduces survival in tumor cells in response to XRT and gemcitabine. VE-822 (80 nM) attenuates ATR signaling in normal cells without enhancing radiation and gemcitabine killing in normal cells. VE-822 (80 nM) increases XRT-induced residual γH2AX and 53BP1 foci compared with XRT in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) pre-treatment decreases Rad51 foci after XRT in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) alone increases the G1-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) abrogates XRT enriched G2/M-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 has little effect alone, while VE-822 (80 nM) combined with XRT and/or gemcitabine enhances early and late apoptosis in PSN-1 cells that is strongest in the triple combination. VE-822 increases tumor response to DNA damaging agents associated with blockade of pChk1 Ser345.


Kinase Assay: Berzosertib is an ATR inhibitor with a Ki value of less than 0.2 nM. It also inhibits ATM with a Ki of 34 nM.


Cell Assay: NSC 613327 (10 nM) is added 24 h pre-XRT and is replaced with fresh medium before addition of Berzosertib (VE-822). PSN-1 cells are treated with Berzosertib (VE-822) (80 nM) for 1 h before, through to 18 h after, XRT (6 Gy). Apoptosis is analyzed 48 h after XRT by flow cytometry using an Annexin V-FITC kit with P.

In VivoVE-822 (60 mg/kg) inhibits phospho-Ser-345-Chk1 in mice bearing PSN-1 tumors after DNA-damaging agents. VE-822 (60 mg/kg) combined with XTR doubles the time for tumors to grow to 600 mm3 of XRT alone in mice bearing both PSN-1 and MiaPaCa-2 tumors. VE-822 (60 mg/kg) added to the combination of gemcitabine and XRT substantially prolongs the tumor growth delay compared with the Gem+XRT1 group n mice bearing both PSN-1 tumors. VE-822 (60 mg/kg) combined with XRT1 increases uptake in tumors by 44% compared with XRT1, suggesting that addition of VE-822 increased γH2AX phosphorylation and persistence of DNA damage caused by XRT.
Animal modelMice bearing PSN-1 or MiaPaCa-2 tumors
Formulation & DosageDissolved in saline; 60 mg/kg; Oral administration
References

Cell Death Dis. 2012 Dec 6;3:e441.