RVX-208
(Synonyms: 阿帕他隆; RVX-208; RVX000222) 目录号 : GC14199
A selective BET bromodomain antagonist
Cas No.:1044870-39-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Competitive Histone Displacement Assay (AlphaScreen Assay) |
Experiments are run on a PHERAstar FS plate reader using an AlphaScreen 680 excitation/570 emission filter set. IC50 values are calculated in Prism 5 after normalization against corresponding DMSO controls. Assays are performed according to the manufacturer’s protocol with minor modifications. |
| Cell experiment [1, 2]: | |
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Cell lines |
Human liver carcinoma HepG2 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
5 μmol/L for 4 h; or 0 to 60 μmol/l for 12, 24, and 48 h |
|
Applications |
HepG2 cells treated with RVX-208 (5 μM) for 4 h only modestly affected BET-dependent gene transcription. Moreover, RVX-208 increased apolipoprotein (apo)A-I and high-density lipoprotein cholesterol (HDL-C) levels in HepG2 cells. |
| Animal experiment [2]: | |
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Animal models |
Na?ve adult male African Green monkeys (AGMs) model |
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Dosage form |
60 mg/kg, oral gavage, once daily for 63 days |
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Applications |
RVX-208 induced elevation of serum apoA-I and HDL-C levels (60% and 97%, respectively) and enhanced cholesterol efflux in vivo. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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 | |
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 (150mg/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.
| Cas No. | 1044870-39-4 | SDF | |
| 别名 | 阿帕他隆; RVX-208; RVX000222 | ||
| 化学名 | 2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-1H-quinazolin-4-one | ||
| Canonical SMILES | CC1=CC(=CC(=C1OCCO)C)C2=NC(=O)C3=C(C=C(C=C3N2)OC)OC | ||
| 分子式 | C20H22N2O5 | 分子量 | 370.4 |
| 溶解度 | ≥ 18.52mg/mL in DMSO | 储存条件 | Store at -20° C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6998 mL | 13.4989 mL | 26.9978 mL |
| 5 mM | 0.54 mL | 2.6998 mL | 5.3996 mL |
| 10 mM | 0.27 mL | 1.3499 mL | 2.6998 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。