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VE-822
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。
VE-822图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
10mg电议
50mg电议
500mg电议
1g电议

产品介绍

Cell lines

Pancreatic ductal adenocarcinoma cell (PDAC)

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

1-2 h

Applications

VE-822 decreases survival of irradiated p53-mutant and K-Ras mutant PDACs. Combination of VE-822 and gemcitabine reduces survival B2–3-fold and significantly more after chemoradiotherapy. In addition, VE-822 increases radation-induced residual gH2AX and 53BP1 foci and decreases Rad51 foci after radiation.

Animal models

Female Balb/c nude mice, pancreatic cancer xenografts

Dosage form

Oral gavage, 60 mg/kg

Preparation method

10% Vitamin E d-alpha tocopheryl polyethylene glycol 1000 succinate

Applications

VE-822 inhibits phospho-Ser-345-Chk1 following treatment of DNA-damaging agents. Combination of VE-822 and radiation significantly prolongs the tumor growth delay compared with the radiation alone. Furthermore, tumor growth delay is substantially longer in the combination group of VE-822+gemcitabine+radiation compared with the combination group of gemcitabine+radiation.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

产品描述

VE-822 is an ATR inhibitor with an IC50 value of 0.019 μM. It is a close analog of VE-821 with a marked increase in potency against ATR.
Radiation (XRT) and chemotherapy induce chromosomal DNA lesions resulting in activation of the ataxia telangiectasiamutated (ATM) and ATM-Rad3-related (ATR) protein kinases in response to double-strand DNA breaks (DSBs) and replication stress, respectively. Defects in the DNA damage response (DDR) such as ATM and p53 deletion/mutation are common in human tumors and occur in up to 70% of patients with PDAC. They might lead to a differential response in DNA repair signaling between normal and tumor cells that could be exploited to increase killing of Radiation (XRT) and chemotherapy induce chromosomal DNA lesions.
In irradiated cancer cells, VE-822 decreased checkpoints of cell-cycle, decreased homologous recombination and increased persistent DNA damage. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity.
Reference:
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 Dis. 2012 Dec 6;3:e441.