CasNo.1232416-25-9,Berzosertib (VE-822),(1232416-25-9) Suppliers

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Purity: >97%

Keywords

Berzosertib (VE-822) VX970, M6620 1232416-25-9

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Biological Activity

Description

Berzosertib (VE-822, VX970, M6620) is an ATR inhibitor with IC50 of 19 nM in HT29 cells.

Features

The first ATR-targeted drug candidate with high selectivity for ATR.

Targets

ATR [1]
(HT29 cells)

19 nM

In vitro

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. [1] VE-822 increases tumor response to DNA damaging agents associated with blockade of pChk1 Ser345. [2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
HCK1T-HPV16	Function Assay	0.5 nM	24 h	enhances E1-dependent replication of the HPV16 genome	25717108
HCK1T-HPV16	Function Assay	0.5 nM	24 h	increases the levels of E1	25717108
MDCK	Cytotoxicity assay	50 nM	72 h	Cytotoxicity against MDCK cells expressing carbonic anhydrase 9 assessed as reduction in cell viability at 50 nM pretreated for 72 hrs followed by 72 hrs incubation under normoxic condition by Alamar blue assay	27823879

Assay

Methods	Test Index	PMID
Western blot	p-STAT3 / STAT3 / AKT / p-AKT; p21 / caspase-3 / PARP / γ-H2AX; PARP / RPA32 / γH2AX / H4 / MEK; WEE1 / p-CDC25c / p-CDK1 / CDK1 / p-CDK2 / CDK2 / RRM1 / RRM2;	29890208 31014753
Growth inhibition assay	Cell viability;	31014753
Immunofluorescence	PD-L1 / Hsp90B1; γH2AX / p53;	30094103 29890208

In vivo

VE-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. [1]