1044870-39-4

Basic information

• Product Name: RVX-208
• Synonyms: 2-(4-(2-hydroxyethoxy)-3,5-diMethylphenyl)-5,7-diMethoxyquinazolin-4(3H)-one;RVX-208;RVX-000222;4(3H)-Quinazolinone, 2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-;2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-4(3H)-quinazolinone RVX-208;Apabetalone;Apabetalone-RVX-208;RVX-208(RVX000222)
• CAS NO: 1044870-39-4
• Molecular Formula: C₂₀H₂₂N₂O₅
• Molecular Weight: 370.39908
• Product Categories: Inhibitors
• Mol File: 1044870-39-4.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 594.2±60.0 °C(Predicted)
• Appearance: /
• Density: 1.28±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C (des.)
• Solubility: Soluble in DMSO (up to 75 mg/ml) or in Ethanol (up to 4 mg/ml).
• PKA: 14.21±0.10(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: RVX-208(CAS DataBase Reference)
• NIST Chemistry Reference: RVX-208(1044870-39-4)
• EPA Substance Registry System: RVX-208(1044870-39-4)

Safety Data

• Hazardous Substances Data: 1044870-39-4(Hazardous Substances Data)

Usage

Description

The bromodomain and extra terminal (BET) proteins interact with acetylated lysine-containing sequences on target proteins via their bromodomains, commonly altering gene transcription. The human BET proteins contain two bromodomains, the first (BD1) being closer to the N-terminus than the second (BD2). RVX-208 is a selective antagonist of BET bromodomains, binding with 10-100-fold higher affinity for BD2 (IC50 = 0.04-0.28 μM) over BD1 (IC50 = 1.8-3.1 μM). RVX-208 causes the selective release of BET proteins from chromatin in cells. It interferes with the BET protein BRD4, resulting in an increased expression of apolipoprotein (Apo) A1 in cells, mice, monkeys, and humans. RVX-208 also reduces atherosclerosis in hyperlipidemic ApoE-deficient mice.

Uses

RVX-208 is a selective antagonist of bromodomain and extra terminal (BET)’s bromodomains.

References

1) Picaud?et al. (2013),?RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain; Proc. Natl. Acad. Sci. USA,?110?19754 2) McLure?et al. (2013),?RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist; PLoS One,?8e83190 3) Bailey?et al. (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 4) Jahagirdar?et al. (2014),?A novel BET bromodomain inhibitor, RVX-208 shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice; Atherosclerosis,?236?91

Upstream product

• 21544-81-0 4,6-dimethoxyindoline-2,3-dione 
• 21577-57-1 2-amino-4,6-dimethoxybenzoic acid 
• 1044872-73-2 4-[2-(tert-butyldimethylsilanyloxy)ethoxy]-3,5-dimethylbenzaldehyde 
• 62827-46-7 2-bromo-4,6-dimethoxybenzamide 
• 20469-65-2 1-bromo-3,5-dimethoxybenzene 
• 81574-69-8 2-bromo-4,6-dimethoxybenzaldehyde 
• 62827-49-0 2-bromo-4,6-dimethoxybenzoic acid 
• 99-10-5 3,5-Dihydroxybenzoic acid 
• 1132-21-4 3,5-dimethoxybenzoic acid 
• 85657-94-9 N-(3,5-dimethoxyphenyl)-2,2,2-trifluoroacetamide 
• 1599437-13-4 N-(2-bromo-3,5-dimethoxybenzene)-2,2,2-trifluoroacetamide 
• 1039948-89-4 4-(2-hydroxy ethoxy)-3,5-dimethyl benzaldehyde 
• 1545025-44-2 2-amino-4,6-dimethoxybenzonitrile 
• 2735-04-8 2,4-Dimethoxyaniline 

Downstream Products

• 1044871-58-0 propylcarbamic acid-2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl ester 
• 1044871-64-8 cyclohexylcarbamic acid-2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl ester 
• 1202407-34-8 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl methanesulfonate 
• 1202407-33-7 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl 4-fluoro-phenylcarbamate 

Relevant articles and documents

Discovery of Orally Bioavailable Chromone Derivatives as Potent and Selective BRD4 Inhibitors: Scaffold Hopping, Optimization, and Pharmacological Evaluation

Bromodomain-containing protein 4 (BRD4) represents a promising drug target for anti-inflammatory therapeutics. Herein, we report the design, synthesis, and pharmacological evaluation of novel chromone derivatives via scaffold hopping to discover a new class of orally bioavailable BRD4-selective inhibitors. Two potent BRD4 bromodomain 1 (BD1)-selective inhibitors 44 (ZL0513) and 45 (ZL0516) have been discovered with high binding affinity (IC50 values of 67-84 nM) and good selectivity over other BRD family proteins and distant BD-containing proteins. Both compounds significantly inhibited the expression of Toll-like receptor-induced inflammatory genes in vitro and airway inflammation in murine models. The cocrystal structure of 45 in complex with human BRD4 BD1 at a high resolution of 2.0 ? has been solved, offering a solid structural basis for its binding validation and further structure-based optimization. These BRD4 BD1 inhibitors demonstrated impressive in vivo efficacy and overall promising pharmacokinetic properties, indicating their therapeutic potential for the treatment of inflammatory diseases.

Design, synthesis and biological evaluation of hypolipidemic compounds based on BRD4 inhibitor RVX-208

Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs.

NITRIC OXIDE-RELEASING PRODRUG MOLECULE

Provided are a type of compounds that can be used for treating cardiovascular diseases and compositions containing the compounds. The compounds and the compositions can improve lipid metabolism disorders by increasing high-density lipoprotein cholesterol in blood; in addition, the compounds and the compositions can also release nitric oxide, and reduce the onset risk of cardiovascular diseases by means of relaxing blood vessels, lowering blood pressure, inhibiting platelet adhesion and aggregation and maintaining vascular tension, and thus play an important role in preventing and treating the occurrence and development of cardiovascular diseases.