| Identification | Back Directory | [Name]
RVX-208 | [CAS]
1044870-39-4 | [Synonyms]
CS-686
CS-1815
RVX-208
RVX-000222
Apabetalone
RVX-208 USP/EP/BP
RVX-208(RVX000222)
Apabetalone-RVX-208
RVX-208(RVX 000222)
APABETALONE; RVX-000222; RVX208; RVX 208; RVX000222; RVX 000222
2-(4-(2-hydroxyethoxy)-3,5-diMethylphenyl)-5,7-diMethoxyquinazolin-4(3H)-one
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 | [Molecular Formula]
C20H22N2O5 | [MDL Number]
MFCD18633270 | [MOL File]
1044870-39-4.mol | [Molecular Weight]
370.399 |
| Chemical Properties | Back Directory | [Boiling point ]
594.2±60.0 °C(Predicted) | [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). | [form ]
solid | [pka]
14.21±0.10(Predicted) | [color ]
White | [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. |
| Hazard Information | Back Directory | [Description]
The bromodomain and extra terminal (BET) proteins interact with acetylated lysine-containing sequences on target proteins via their bromodomains, commonly altering gene transcription.1 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).2,3 RVX-208 causes the selective release of BET proteins from chromatin in cells.2,3 It interferes with the BET protein BRD4, resulting in an increased expression of apolipoprotein (Apo) A1 in cells, mice, monkeys, and humans.4,5 RVX-208 also reduces atherosclerosis in hyperlipidemic ApoE-deficient mice.5 | [Uses]
RVX-208 is a selective antagonist of bromodomain and extra terminal (BET)’s bromodomains. | [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 Apabetalone (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 Apabetalone 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 Apabetalone 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 Apabetalone. Compared to the vehicle control animals, Apabetalone 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]. | [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 |
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