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RVX-208

现货
Catalog No.
B1499
BET bromodomain抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 750.00
现货
5mg
¥ 680.00
现货
20mg
¥ 1,890.00
现货

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Background

RVX-208 is a potent inhibitor of bromodomain with IC50 values of 0.51 and 87 μM for BD2 and BD1, respectively [1].

Bromodomains (BRDs) are protein-interaction modules that bind to ε-N-acetylated lysine-containing proteins. BRDs act as effector domains of chromatin-modifying enzymes, transcriptional regulators and chromatin modulators [1].

RVX-208 is a potent second BET bromodomains inhibitor. RVX-208 exhibited affinity with KD values of 0.194 and 4.06 for BD2 and BD1, respectively. RVX-208 bound to the acetyl-lysine binding pocket in a peptide-competitive way [1]. In HepG2 cells, RVX-208 induced messenger ribonucleic acid and protein synthesis of apolipoprotein (apo)A-I [2]. RVX-208 induced ApoA-I mRNA mediated by BRD4 [3].

In African green monkeys, RVX-208 increased serum HDL-C and apoA-I levels by 97% and 60%, respectively. Also, RVX-208 increased the levels of pre-β1-LpA-I, α1-LpA-I HDL-subparticles, adenosine triphosphate binding cassette G1, adenosine triphosphate binding cassette AI and cholesterol efflux [2]. In hyperlipidemic apoE(-/-) mice, RVX-208 (150?mg/kg) significantly inhibited aortic lesion. Also, RVX-208 increased HDL-C and reduced LDL-C and proinflammatory cytokines [4].

References:
[1].  Picaud S, Wells C, Felletar I, et al. RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. Proc Natl Acad Sci U S A, 2013, 110(49): 19754-19759.
[2].  Bailey D, Jahagirdar R, Gordon A, et al. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol, 2010, 55(23): 2580-2589.
[3].  McLure KG, Gesner EM, Tsujikawa L, et al. RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist. PLoS One, 2013, 8(12): e83190.
[4].  Jahagirdar R, Zhang H, Azhar S, et al. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice. Atherosclerosis, 2014, 236(1): 91-100.

文献引用

1. Zhao L, Li J, et al. "Photoreceptor protection via blockade of BET epigenetic readers in a murine model of inherited retinal degeneration." J Neuroinflammation. 2017 Jan 19;14(1):14. PMID:28103888
2. Alonso, Victoria Lucia, et al. "Overexpression of bromodomain factor 3 in Trypanosoma cruzi (TcBDF3) affects differentiation of the parasite and protects it against bromodomain inhibitors." FEBS Journal (2016). PMID:27007774

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt370.4
Cas No.1044870-39-4
FormulaC20H22N2O5
Solubility≥18.52mg/mL in DMSO
Chemical Name2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-1H-quinazolin-4-one
SDFDownload SDF
Canonical SMILESCC1=CC(=CC(=C1OCCO)C)C2=NC(=O)C3=C(C=C(C=C3N2)OC)OC
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。
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。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

竞争性组蛋白取代试验(AlphaScreen 试验)

实验使用AlphaScreen 680激发/570发射滤光片组在PHERAstar FS酶标仪上进行。对相应DMSO对照标准化后,IC50值在Prism 5中计算。实验测定根据稍加修改的生产商方案进行。

细胞实验 [1, 2]:

细胞系

人源肝癌细胞 HepG2

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

5 μmol/L处理4 h; 或0 - 60μmol/l处理12、24与48 h

应用

利用RVX-208 (5 μM)处理HepG2细胞4 h仅中等程度的影响BET相关基因的转录。同时,RVX-208 处理HepG2后增加其载脂蛋白(Apo A-I)和高密度脂蛋白胆固醇(HDL-C)的表达水平。

动物实验 [2]:

动物模型

当地成年雄性非洲绿猴(AGM)模型

剂量

60 mg/kg,口服给药,一天一次,持续63天

应用

RVX-208在体内诱导载脂蛋白(Apo A-I)和高密度脂蛋白胆固醇(HDL-C)的表达水平的增加,分别增加60%和97%,并且促进胆固醇的外流。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1. Picaud, S., Wells, C., Felletar, I., Brotherton, D., Martin, S., Savitsky, P., Diez-Dacal, B., Philpott, M., Bountra, C., Lingard, H., Fedorov, O., Muller, S., Brennan, P. E., Knapp, S. and Filippakopoulos, P. (2013) RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. Proc Natl Acad Sci U S A. 110, 19754-19759

2. Bailey, D., Jahagirdar, R., Gordon, A., Hafiane, A., Campbell, S., Chatur, S., Wagner, G. S., Hansen, H. C., Chiacchia, F. S., Johansson, J., Krimbou, L., Wong, N. C. and Genest, J. (2010) RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol. 55, 2580-2589

生物活性

描述 RVX-208是一种有效的BET bromodomain抑制剂,作用于BD2,IC50值为0.51 μM。
靶点 BD2          
IC50 0.51 μM          

质量控制

化学结构

RVX-208

相关生物数据

RVX-208

相关生物数据

RVX-208

相关生物数据

RVX-208