RVX-208
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
RVX-208是一种有效的bromodomain抑制剂，作用于BD2和BD1，IC50值分别为0.51 和87 μM[1]。
Bromodomains（BRDs）是与蛋白质相互作用的模块，与包含ε-N-乙酰赖氨酸的蛋白质结合。BRDs充当染色质修饰酶、转录调节子和染色质调节子的效应器结构域[1]。
RVX-208是一种有效的第二类BET bromodomains抑制剂。RVX-208表现出对BD2和BD1的亲和力，KD值分别为0.194和4.06。RVX-208以多肽竞争的方式与乙酰赖氨酸的结合口袋相结合[1]。在HepG2细胞中，RVX-208诱导载脂蛋白（apo）A-I的信使核糖核酸和蛋白合成[2]。RVX-208诱导BRD4介导的ApoA-I mRNA[3]。
在非洲绿猴中，RVX-208 分别增加了97%和60%的血清HDL-C和apoA-I水平。RVX-208也增加预β1-LpA-I、α1-LpA-I HDL亚微粒子、三磷酸腺苷结合盒转运体G1、三磷酸腺苷结合盒转运体AI和胆固醇外流[2]。在高脂血症apoE(-/-)小鼠中，RVX-208（150 mg/kg）显著抑制主动脉病变。此外，RVX-208增加HDL-C，减少LDL-C和促炎细胞因子[4]。
参考文献：
[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.
- 1. Yi Zhao, Takuro Shirasu, et al. "Biomimetic, ROS-detonable nanoclusters—A multimodal nanoplatform for anti-restenotic therapy." J Control Release. 2021 Oct 10;338:295-306. PMID: 34416322
- 2. 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
- 3. 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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 370.4 |
| Cas No. | 1044870-39-4 |
| Formula | C20H22N2O5 |
| Solubility | insoluble in H2O; ≥18.52 mg/mL in DMSO; ≥2.48 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-1H-quinazolin-4-one |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC(=CC(=C1OCCO)C)C2=NC(=O)C3=C(C=C(C=C3N2)OC)OC |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 激酶实验 [1]: | |
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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]: | |
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细胞系 |
人源肝癌细胞 HepG2 |
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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。 |
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反应时间 |
5 μmol/L处理4 h; 或0 - 60μmol/l处理12、24与48 h |
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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]: | |
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动物模型 |
当地成年雄性非洲绿猴（AGM）模型 |
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剂量 |
60 mg/kg，口服给药，一天一次，持续63天 |
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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。 |
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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。 |
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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 |
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| 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 | |||||
质量控制和MSDS
- 批次：
化学结构
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