"目录号: HY-14731
Cell Cycle/DNA DamagePI3K/Akt/mTOR-
VE-821 是一种有效的 ATP 竞争性的ATR抑制剂，Ki/IC50为 13 nM/26 nM。
ATM/ATR
相关产品
Wortmannin-AZD6738-VE-822-KU-55933-KU-60019-AZD0156-CP-466722-AZ20-CGK733-ETP-46464-HLM006474-BAY-1895344 hydrochloride-
生物活性
Description
VE-821 is a potent ATP-competitive inhibitor ofATRwithKi/IC50of 13 nM/26 nM.
IC50& Target
Ki: 13 nM (ATR)[1]
IC50: 26 nM (ATR)[2]
In Vitro
VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3Kγ (Kis of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively) and against a large panel of unrelated protein kinases[1]. VE-821 also inhibits ATM and DNA-PK wirh IC50of >8 μM, and 4.4 μM, respectively[2]. VE-821 significantly enhances the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and Gemcitabine under both normoxic and hypoxic conditions. ATR inhibition by VE-821 leads to inhibition of radiation-induced G2/M arrest in cancer cells. In both PSN-1 and MiaPaCa-2 cells, 1 μM VE-821 inhibits phosphorylation of Chk1 (Ser 345) after treatment with Gemcitabine (100 nM), radiation (6 Gy) or both, at 2 h post-irradiation[3].
References
[1].Reaper PM, et al. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011 Apr 13;7(7):428-30.
[2].Charrier JD, et al. Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J Med Chem. 2011 Apr 14;54(7):2320-30.
[3].Prevo R, et al. 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.
[4].Muralidharan SV, et al. BET bromodomain inhibitors synergize with ATR inhibitors to induce DNA damage, apoptosis, senescence-associated secretory pathway and ER stress in Myc-induced lymphoma cells. Oncogene. 2016 Sep 8;35(36):4689-97.