Apabetalone (RVX-08, RVX-000222)

Alias: RVX-000222; RVX208; RVX 000222; RVX 208; RVX000222; RVX-208; Apabetalone.
Cat No.:V0415 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.
Apabetalone (RVX-08, RVX-000222) Chemical Structure CAS No.: 1044870-39-4
Product category: Epigenetic Reader Domain
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
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].
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].
Animal Protocol
Dissolved in 1N HCl and carboxymethyl cellulose; 60mg/kg; i.v. injection or p.o.
Na ve adult male AGMs
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
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H22N2O5
Molecular Weight
370.4
CAS #
1044870-39-4
Related CAS #
1044870-39-4
Appearance
Typically exists as solids (or liquids in special cases) at room temperature
SMILES
O=C1NC(C2=CC(C)=C(OCCO)C(C)=C2)=NC3=C1C(OC)=CC(OC)=C3
InChi Key
NETXMUIMUZJUTB-UHFFFAOYSA-N
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)
Chemical Name
2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one
Synonyms
RVX-000222; RVX208; RVX 000222; RVX 208; RVX000222; RVX-208; Apabetalone.
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: 74 mg/mL (199.8 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


Solubility in Formulation 4: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 5: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 6: ≥ 0.5 mg/mL (1.35 mM) (saturation unknown) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 7: 0.5% CMC Na (1N HCl, PH 2.5-3.0):8 mg/mL

Solubility in Formulation 8: 15.15 mg/mL (40.90 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

 (Please use freshly prepared in vivo formulations for optimal results.)
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.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03655704 Completed Drug: Apabetalone Pulmonary Arterial Hypertension Steeve Provencher August 22, 2019 Early Phase 1
NCT04915300 Not yet recruiting Drug: Apabetalone
Drug: Placebo
Pulmonary Arterial Hypertension Laval University October 2023 Phase 2
NCT04894266 Terminated Drug: Apabetalone
Other: Standard of care
COVID-19 Infection Resverlogix Corp January 14, 2022 Phase 2
Phase 3
NCT03160430 Not yet recruiting Drug: apabetalone
Drug: Placebos
Kidney Failure, Chronic Resverlogix Corp November 22, 2024 Phase 1
Phase 2
Biological Data
  • RVX-208

  • RVX-208
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