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5mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Other Sizes |
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Purity: ≥98%
Apabetalone (also known as RVX-208, RVX000222) is a novel and potent inhibitor of BET (Bromodomain and Extra-Terminal) bromodomain (BD) with potential anti-inflammatory activity and the potential to be used in the treatment of cardiovascular diseases. It inhibits BET (BD2) with an IC50 of 0.510 μM in a cell-free assay, and shows about 170-fold higher selectivity for BD2 over BD1. RVX-208 is currently undergoing phase III clinical trials for reducing the relative risk (RR) of major adverse cardiac events (MACE) in patients with cardiovascular disease (CVD). It acts by binding to the acetyl-lysine binding pocket in a peptide-competitive way. In HepG2 cells, RVX-208 induced messenger ribonucleic acid and protein synthesis of apolipoprotein (apo)A-I.
ln Vitro |
Apabetalone (RVX-208) competes with binding of an acetylated histone peptide to tandem BD1 BD2 protein constructions of the four BET proteins, exhibiting IC50s between 0.5 and 1.8 µM. Apabetalone promotes the formation of ApoA-I in hepatocytes in vitro, which leads in increased high density lipoprotein cholesterol (HDL-C). Apabetalone predominantly binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a position bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological effect. increases Apolipoprotein AI (ApoA-I) synthesis through an epigenetic mechanism and shows that BET inhibition may be a promising new approach to the treatment of atherosclerosis. Apabetalone promotes ApoA-I expression in liver cells[2].
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ln Vivo |
In the study design for the preventive treatment of atherosclerosis, mice are given a Western diet along with 150 mg/kg/dose bid of medication for a duration of 12 weeks. A year after therapy, mice are killed. Both the vehicle treated and the Apabetalone (RVX-208) treated groups show a progressive increase in body weight. After 12 weeks on a Western diet, the Apabetalone treated group's body weight increased by 4 g (from 24 g to 28 g), while the vehicle treated group experienced a 9 g gain (from 25 g to 34 g). The notable reduction in body weight increase observed in mice treated with Apabetalone is not attributable to a decrease in feed intake, indicating a favorable characteristic of the compound. After six and twelve weeks of therapy with either the vehicle or apibetalone, plasma lipid measurements are performed. At six weeks into therapy, mice treated with apibetalone had a considerable rise (~200%) in their HDL-C levels compared to the vehicle control animals. This increase persisted until the 12-week study's conclusion[3].
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Animal Protocol |
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References |
[1]. Picaud S, et al. RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19754-9.
[2]. McLure KG, et al. RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist. PLoS One. 2013 Dec 31;8(12):e83190. [3]. Jahagirdar R, et al. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice. Atherosclerosis. 2014 Sep;236(1):91-100 |
Molecular Formula |
C20H22N2O5
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Molecular Weight |
370.4
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CAS # |
1044870-39-4
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SMILES |
O=C1NC(C2=CC(C)=C(OCCO)C(C)=C2)=NC3=C1C(OC)=CC(OC)=C3
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InChi Key |
NETXMUIMUZJUTB-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C20H22N2O5/c1-11-7-13(8-12(2)18(11)27-6-5-23)19-21-15-9-14(25-3)10-16(26-4)17(15)20(24)22-19/h7-10,23H,5-6H2,1-4H3,(H,21,22,24)
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Chemical Name |
2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one
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Synonyms |
RVX-000222; RVX208; RVX 000222; RVX 208; RVX000222; RVX-208; Apabetalone.
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6998 mL | 13.4989 mL | 26.9978 mL | |
5 mM | 0.5400 mL | 2.6998 mL | 5.3996 mL | |
10 mM | 0.2700 mL | 1.3499 mL | 2.6998 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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