VE-821

Short Summary : ATR kinase inhibitor

Category : Cell Cycle/Checkpoint|ATM/ATR

Purity : 0.9853

CAS Number : 1232410-49-9

Formula : C18H16N4O3S

Molecular Weight : 368.41

SMILE : CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C(=O)NC3=CC=CC=C3)N

Solubility : >18.4mg/mL in DMSO

Storage : Store at -20°C

Description : VE-821 is a potent, highly-selective, and ATP-competitive DNA damage response (DDR) kinase ATR inhibitor with Ki value of 13nM. VE-821 specifically inhibits ATR, revealing low cross-reactivity against the mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), phosphoinositol 3-kinase- (PI3K) and the related PIKKs ATM [1].
HL-60 cells treated with VE-821 (10M) showed reduction of phosphorylatin of Chk1 (Ser 345), inhibition of cell growth, and a radiosensitizing effect after Gamma-ray irradiation [2].
VE-821 has also been demonstrated to down-regulate the phosphorylated Chk1 (Ser 345) but it does not inhibit the phosphorylation of Chk2 (Thr68) and ATM (Ser1981) in pancreatic cancer cell lines, including PSN-1 and MiaPaCa-2 cells that are treated with gemcitabine or radiation. VE-821 combined with gemcitabine (a nucleoside analog) has caused a remarkable increase of cytotoxic effect of gemcitabine against hypoxia [3].
References:
[1] Reaper PM1, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011 Apr 13;7(7):428-30.
[2] Vvrov J1, Zrybnick L, Luk ov E, ez ov M, Novotn E, Sinkorov Z, Tichy A, Pejchal J, Duri ov K. Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60). Radiat Environ Biophys. 2013 Nov;52(4):471-9.
[3] Prevo R1, Fokas E, Reaper PM, Charlton PA, Pollard JR, McKenna WG, Muschel RJ, Brunner TB.The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012 Sep;13(11):1072-81.

Download datasheet