RVX-208 |
| Catalog No.: GC14199 |
RVX-208 (RVX-208) is an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. The IC50s are 87 μM and 0.51 μM for BD1 and BD2, respectively.
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
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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. |
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Reacting condition |
5 μmol/L for 4 h; or 0 to 60 μmol/l for 12, 24, and 48 h |
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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 |
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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 | |
| Chemical Name | 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 | ||
| Formula | C20H22N2O5 | M.Wt | 370.4 |
| Solubility | ≥ 18.52mg/mL in DMSO | Storage | Store at -20° C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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