1. Epigenetics
  2. Epigenetic Reader Domain

RVX-208 (Synonyms: Apabetalone; RVX000222)

Cat. No.: HY-16652 Purity: 99.19%
Data Sheet SDS Handling Instructions

RVX-208 is an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. The IC50s are 87±10 μM and 0.51±0.041 μM for BD1 and BD2, respectively.

For research use only. We do not sell to patients.
RVX-208 Chemical Structure

RVX-208 Chemical Structure

CAS No. : 1044870-39-4

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $75 In-stock
5 mg $68 In-stock
10 mg $100 In-stock
50 mg $350 In-stock
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Customer Review

    RVX-208 purchased from MCE. Usage Cited in: Biochim Biophys Acta. 2016 Dec;1859(12):1527-1537.

    RVX208 increases CTGF and CYR61 expression and TAZ protein level in HCT116 cells.

    RVX-208 purchased from MCE. Usage Cited in: Biochim Biophys Acta. 2016 Dec;1859(12):1527-1537.

    JQ1 treatment decreases β-catenin levels in HCT116 cells, but increases TAZ protein. When cells reach confluence, they are serum-starved overnight and pretreated with DMSO or JQ1 (500 nM) for 1 hour, followed by growth medium (containing 10% serum) stimulation for 24 hours.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    RVX-208 is an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. The IC50s are 87±10 μM and 0.51±0.041 μM for BD1 and BD2, respectively.

    IC50 & Target

    IC50: 510±41 nM (BD2), 87±10 μM (BD1)[1]

    In Vitro

    RVX-208 competes with binding of an acetylated histone peptide to tandem BD1 BD2 protein constructs of the four BET proteins, with IC50s between 0.5 and 1.8 µM. RVX-208 increases the production of ApoA-I in hepatocytes in vitro, which results in increased high density lipoprotein cholesterol (HDL-C). RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. RVX-208 increases Apolipoprotein A-I (ApoA-I) production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis. RVX-208 increases ApoA-I expression in liver cells[2].

    In Vivo

    In the atherosclerosis prophylactic treatment study design, mice are fed a Western diet concurrent with the treatment with 150 mg/kg/dose b.i.d. for 12 weeks. Mice are sacrificed at 12 weeks after treatment. There is a progressive increase in body weight in both the vehicle treated as well as the RVX-208 treated groups. However, there is only an increase of 4 g (from 24 g to 28 g) body weight after 12 weeks on Western diet in the RVX-208 treated group whereas this increase is found to be 9 g (25 g-34 g) in the vehicle treated group. The significant decrease in body weight gain in RVX-208 treated mice is not due to decreased feed consumption, suggesting a positive attribute of the molecule. Plasma lipid measurements are done at 6 weeks and 12 weeks of treatment with either the vehicle or RVX-208. Compared to the vehicle control animals, RVX-208 treated mice show significant increase (~200%) in the levels of HDL-C at 6 weeks of treatment, which is sustained until end of the study (12 weeks)[3].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT03160430 Resverlogix Corp Kidney Failure, Chronic September 15, 2017 Phase 1|Phase 2
    NCT03160430 Resverlogix Corp Kidney Failure, Chronic September 15, 2017 Phase 1|Phase 2
    NCT01728467 Resverlogix Corp|Baker IDI Heart and Diabetes Institute|Nucleus Network Ltd Diabetes November 2012 Phase 2
    NCT03228940 Resverlogix Corp Fabry Disease October 30, 2017 Phase 1|Phase 2
    NCT01058018 Resverlogix Corp Atherosclerosis|Coronary Artery Disease December 2009 Phase 2
    NCT01863225 Resverlogix Corp|South Australian Health and Medical Research Institute Dyslipidemia|Coronary Artery Disease May 2013 Phase 2
    NCT00768274 Resverlogix Corp Dyslipidemia|Atherosclerosis|Acute Coronary Syndrome|Cardiovascular Disease September 2008 Phase 1|Phase 2
    NCT02586155 Resverlogix Corp|PPD|ICON plc|Medidata Solutions Diabetes Mellitus, Type 2|Coronary Artery Disease|Cardiovascular Diseases October 2015 Phase 3
    NCT01423188 Resverlogix Corp|The Cleveland Clinic Coronary Artery Disease|Dyslipidemia August 2011 Phase 2
    NCT01067820 Resverlogix Corp|The Cleveland Clinic Coronary Artery Disease September 2011 Phase 2
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    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 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
    Cell Assay
    [2]

    RVX-208 is prepared in DMSO and stored, and then diluted with appropriate medium before use[2].

    Huh7 cells are plated at 23,000/well in a 96 well plate in DMEM+10% FBS before allowing to grow overnight. Cells are treated with compounds for 48 h in 0.1% DMSO with or without 5 µM Actinomycin D. U937 cells are differentiated for 3 days in 60 ng/mL PMA, 32,000 cells/well in 96-well format. Cells are then treated with compound in 0.1% DMSO in RPMI media+10% FBS, and after 1 h, lipopolysaccharide is added to the cells at 1 µg/mL for 3 hours[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [3]

    RVX-208 is prepared as a suspension in a Polyethylene glycol-300/polysorbate-80 based vehicle after pH adjustment to 2.5-3[3].

    Mice[3]
    Seven to eight week old male ApoE-/- mice are used. Based on the body weight and lipid values, mice are divided into 2 groups (n=12): group 1, vehicle; and group 2, test agent, RVX-208. Mice are then switched to Western diet (0.15% cholesterol and 42% calories from fat) and concurrently treated orally by gavage with either vehicle or the test agent, RVX-208 (150 mg/kg/dose b.i.d) for 12 weeks. After 6 week of treatment, an interim blood draw is done to monitor serum lipid levels. After 12 weeks of treatment mice are sacrificed to measure blood lipid parameters, aortic lesion, and liver and aortic RNA. Eight mice are used for enface (aortic plaque) analysis, 4 mice for tissue collection for mRNA and all 12 mice used for aortic sinus lesion area measurement. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    370.4

    Formula

    C₂₀H₂₂N₂O₅

    CAS No.

    1044870-39-4

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 33 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Inquiry Information

    Product Name:
    RVX-208
    Cat. No.:
    HY-16652
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