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In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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.
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
10% Vitamin E d-alpha tocopheryl polyethylene glycol 1000 succinate
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.
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 Dis. 2012 Dec 6;3:e441.
