VE-821_ATR激酶抑制剂_1232410-49-9_Apexbio

VE-821ATR激酶抑制剂

Evaluation Sample 客户使用Apexbio产品发表的文献

质量控制

质量控制和MSDS

COA (Certificate Of Analysis)

HPLC

NMR (Nuclear Magnetic Resonance)

MSDS (Material Safety Data Sheet)

化学性质

CAS号1232410-49-9SDF Download SDF

化学名2-(aminomethyl)-6-[4,6-diamino-3-[4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol;sulfuric acid SMILES CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C(=O)NC3=CC=CC=C3)N

分子式C18H16N4O3S分子量368.41

溶解性Soluble in DMSO > 10 mM储存条件Store at -20°C

一般建议为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。储液可以在零下20℃中保存数月。

运输条件试用装：蓝冰运输。

其他可选规格：常温运输或根据您的要求用蓝冰运输。

生物活性

描述VE-821是一种有效的、选择性的和ATP竞争性的ATR激酶抑制剂，Ki/IC50值分别为13 nM/26 nM。靶点ATR

IC5013 nM/26 nM (K i/IC50 )

研究更新

1. 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. doi:

10.4161/cbt.21093. Epub 2012 Jul 24.

Abstract

The ATR inhibitor VE-821 significantly sensitized a few pancreatic cancer cells to DNA damaging agents, radiotherapy and gemcitabine, where IT inhibited Chk1 phosphorylation and homologous recombination repair, triggered inhibition of G 2/M arrest, reduced radiosurvival and increased DNA damage in radiation- and

gemcitabine-treated cancer cells.

2. 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. doi: 10.1007/s00411-013-0486-5. Epub 2013 Aug 11.

Abstract

The ATR inhibitor VE-821 exerted a more pronounced radiosenstizing effect in HL-60 cells, where it reduced phosphorylation of check-point kinase 1 and the repair of the radiation damage, inhibited G2 cell cycle arrest and induced apoptosis.

产品描述

VE-821是一种有效的、高选择性的和ATP竞争性的DNA损伤响应激酶ATR抑制剂，Ki值为13 nM。VE-821特异性地抑制ATR，与mTOR、DNA依赖性蛋白激酶（DNA-PK）、磷酸

肌醇3-激酶γ（PI3K）和相关的PIKKs ATM具有低交叉反应性[1]。

在HL-60细胞中，VE-821 (10 μM) 减少Chk1 （Ser 345）的磷酸化，抑制细胞生长，并具有放射增敏作用[2]。在胰腺癌细胞系（包括gemcitabine或放射处理的PSN-1和MiaPaCa-2细胞）中，VE-821下调磷酸化的Chk1 (Ser 345)，但不能抑制Chk2 (Thr68)和ATM (Ser1981)的磷酸化。VE-821与gemcitabine（核苷类似物）联合使用显著增加gemcitabine抗缺氧的细胞毒性效应[3]。

参考文献：

[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] Vávrová J1, Zárybnická L, Luká?ová E, ?ezá?ová M, Novotná E, Sinkorová Z, Tichy A, Pejchal J, Duri?ová 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.