VE-821 是一种有效的 ATP 竞争性的 ATR 抑制剂

VE-821  

VE-821 是一种有效的 ATP 竞争性的 ATR 抑制剂，K_i/IC₅₀ 为 13 nM/26 nM。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
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生物活性    
VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM.

体外研究
(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 (compound 27) also inhibits ATM and DNA-PK wirh IC50 of >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].

分子量    
368.41

性状    
Solid

Formula    
C18H16N4O3S

CAS 号    
1232410-49-9

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 50 mg/mL (135.72 mM; Need ultrasonic)

H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.7144 mL    13.5718 mL    27.1437 mL
5 mM    0.5429 mL    2.7144 mL    5.4287 mL
10 mM    0.2714 mL    1.3572 mL    2.7144 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
1.
VE-821 is prepared im vehicle (10% PEG300, 2.5% Tween-80, pH 4)
 

参考文献

[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. [Content Brief] [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.  [Content Brief] [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.  [Content Brief] [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.  [Content Brief]