RVX-208 is a potent and selective BET bromodomain inhibitor with an IC₅₀ of 0.51 μM for the second bromodomain (BD2), which is about 170-fold selectivity over BD1. RVX 208 binds to the acetyl-lysine binding pocket in a peptide-competitive manner, increases apoA-I and HDL-C in vitro and in vivo. In AGMs, RVX-208 raises serum pre-beta(1)-LpA-I and alpha-LpA-I levels and enhances cholesterol efflux. RVX-208 is the first-in-class BD2-selective inhibitor of BET bromodomain tested in Phase II clinical trials for treatment of coronary syndromes and atherosclerosis.

How to Use:

• In vitro: RVX-208 was used at 10 µM final concentration in various in vitro assays.
• In vivo: RVX-208 was dosed to naïve ***** male African green monkeys (AGMs) by oral gavage or intravenous administration at 60 mg/kg once per day.

Reference:

1. 1. Bailey D, et al. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. (2010) J Am Coll Cardiol. 55(23):2580-9.
2. 2. Picaud S, et al. RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. (2013) Proc Natl Acad Sci USA. 110(49):19754-9.
3. 3. McLure KG, et al. RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist. (2013) PLoS One. 8(12):e83190.