RVX-208

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.

target

BD2

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