General
Preferred name
APABETALONE
Synonyms
RVX000222 ()
RVX-208 ()
RVX 208 ()
Apabetalone (RVX-208) ()
RVX-000222 ()
P&D ID
PD010360
CAS
1044870-39-4
Tags
available
obsolete probe
drug candidate
Drug Status
investigational
Max Phase
Phase 3
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Apabetalone (RVX 208) is a derivative of the plant polyphenol . RVX 208 is an investigational inhibitor of BET bromodomain containing proteins, with potential anti-atherosclerotic action for the treatment of cardiovascular disease (CVD) .
SARS-CoV-2 and CIVID-19: Apabetalone (RVX 208) has been reported to reduce ACE2 expression and hence SARS-CoV-2 infection in vitro , and to block inflammation-mediated cardiac injury and dysfunction that is caused by SARS-CoV-2 infection (in a study using human cardiac organoids) . It has been respositioned for potential to provide a cardio-protective therapy that prevents COVID-19-mediated cardiac damage. (GtoPdb)
SARS-CoV-2 and CIVID-19: Apabetalone (RVX 208) has been reported to reduce ACE2 expression and hence SARS-CoV-2 infection in vitro , and to block inflammation-mediated cardiac injury and dysfunction that is caused by SARS-CoV-2 infection (in a study using human cardiac organoids) . It has been respositioned for potential to provide a cardio-protective therapy that prevents COVID-19-mediated cardiac damage. (GtoPdb)
DESCRIPTION
RVX-208 is a potent inhibitor of BET bromodomains. RVX-208 functions by removing atherosclerotic plaque via reverse cholesterol transport (RCT). RVX-208 increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that 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. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
7
Organisms
0
Compound Sets
15
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
Guide to Pharmacology
IPPI - DB
MedChem Express Bioactive Compound Library
Novartis Chemogenetic Library (NIBR MoA Box)
Obsolete Compounds
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
28
Molecular Weight
370.15
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
6
Ring Count
3
Aromatic Ring Count
3
cLogP
2.6
TPSA
93.67
Fraction CSP3
0.3
Chiral centers
0.0
Largest ring
6.0
QED
0.69
Structural alerts
1
historic compounds (Chemical Probes.org)
Obsolete
Related compounds
Custom attributes
(extracted from source data)
Pathway
Chromatin/Epigenetic
Anti-infection
Epigenetics
Target
BD2
BRD3
BET inhibitor
Epigenetic Reader Domain
HIV
Member status
member
MOA
BRD2/3/4/T BET familiy inhibitor
APOA1 Expression Enhancers
BRD4 inhibitor
apolipoprotein expression enhancer
Solubility
In Vitro:<br/>DMSO : ≥ 33 mg/mL(89.09 mM)<br/>In Vivo:<br/>1.Add each solvent one by one:10% DMSO >> 40%PEG300 >> 5%Tween-80 >> 45% saline<br/>Solubility: ≥ 2.5 mg/mL (6.75 mM)
Clear solution<br/>2.Add each solvent one by one:10% DMSO >> 90% (20%SBE-β-CDin saline)<br/>Solubility: ≥ 2.5 mg/mL (6.75 mM)
Clear solution<br/>3.Add each solvent one by one:10% DMSO >> 90%corn oil<br/>Solubility: ≥ 2.5 mg/mL (6.75 mM)
Clear solution<br/>4.Add each solvent one by one:5% DMSO >> 40%PEG300 >> 5%Tween-80 >> 50% saline<br/>Solubility: ≥ 2.5 mg/mL (6.75 mM)
Clear solution<br/>5.Add each solvent one by one:5% DMSO >> 95% (20%SBE-β-CDin saline)<br/>Solubility: ≥ 2.5 mg/mL (6.75 mM)
Clear solution<br/>6.Add each solvent one by one:1% DMSO >> 99% saline<br/>Solubility: ≥ 0.5 mg/mL (1.35 mM)
Clear solution
Source data
