VE-822


CAS No. : 1232416-25-9

VE-822,1232416-25-9
Product Details
For research use only. Not Intended for Therapeutic Use!
Cat No:I000916
Synonyms:3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine
Molecular Formula:C₂₄H₂₅N₅O₃S
Molecular Weight:463.55
Target:ATM/ATR
IC50:0.2 nM (Ki); 19 nM (Cell IC50)
Price:Get quote
We would like to match the lowest price on market if possible.

Your information is safe with us.

refresh
Appearance:Yellow solid powder
Purity: > 98%
Cat No:I000916
Cas No:1232416-25-9
Product-Name:VE-822
InChI: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)
InChIKey:JZCWLJDSIRUGIN-UHFFFAOYSA-N
SMILES:CC(C)S(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C3=CC(=NO3)C4=CC=C(C=C4)CNC)N

VE-822(cas 1232416-25-9) is a selective ATR inhibitor with an Ki value of 0.2 nM, >150 fold selectivity over ATM (Ki=34 nM), DNA-PK (Ki >4 uM) and mTOR (Ki >1 uM).
VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. 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. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC.

1. Cell Death Dis. 2012 Dec 6;3:e441. doi: 10.1038/cddis.2012.181.

Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.

Fokas E(1), Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, Vallis KA, Hammond EM, Olcina MM, Gillies McKenna W, Muschel RJ, Brunner TB.
Author information:
(1)Gray Institute for Radiation Oncology and Biology, Oxford University, Oxford, UK.

Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We tested VE-822, an ATR inhibitor, for in vitro and in vivo radiosensitization. Chk1 phosphorylation was used to indicate ATR activity, γH2AX and 53BP1 foci as evidence of DNA damage and Rad51 foci for homologous recombination activity. Sensitivity to radiation (XRT) and gemcitabine was measured with clonogenic assays in vitro and tumor growth delay in vivo. Murine intestinal damage was evaluated after abdominal XRT. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. 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. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC.
Related Products
  • CAS No. :1198097-97-0
    Product Name:

    Mirin

    Cat No: I000727 View details
  • CAS No. :905973-89-9
    Product Name:

    CGK733

    Cat No: I005413 View details
  • CAS No. :587871-26-9
    Product Name:

    ATM Kinase Inhibitor, KU-55933

    Cat No: I004201 View details
  • CAS No. :1232410-49-9
    Product Name:

    VE-821

    Cat No: I000915 View details