Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C20H22N2O5 |
| Molecular Weight | 370.3991 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(OC)=C2C(=O)NC(=NC2=C1)C3=CC(C)=C(OCCO)C(C)=C3
InChI
InChIKey=NETXMUIMUZJUTB-UHFFFAOYSA-N
InChI=1S/C20H22N2O5/c1-11-7-13(8-12(2)18(11)27-6-5-23)19-21-15-9-14(25-3)10-16(26-4)17(15)20(24)22-19/h7-10,23H,5-6H2,1-4H3,(H,21,22,24)
| Molecular Formula | C20H22N2O5 |
| Molecular Weight | 370.3991 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: Description was created using several sources including: https://clinicaltrials.gov/ct2/show/NCT02586155?term=APABETALONE&rank=3 | https://www.ncbi.nlm.nih.gov/pubmed/24391744 | https://www.ncbi.nlm.nih.gov/pubmed/?term=27570805
Curator's Comment: Description was created using several sources including: https://clinicaltrials.gov/ct2/show/NCT02586155?term=APABETALONE&rank=3 | https://www.ncbi.nlm.nih.gov/pubmed/24391744 | https://www.ncbi.nlm.nih.gov/pubmed/?term=27570805
Apabetalone (RVX-208) is a small molecule BET bromodomain inhibitor selective for BRD4-BD2 undergoing clinical development as a potential therapy to enhance ApoA-I production and treat atherosclerosis and prevent cardiovascular disease events. Apabetalone increases apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-Cholesterol) in vitro and in vivo which is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increased the Tm of all BET bromodomains, indicative of binding. RVX-208 competes for acetylated histone H4 peptide binding to both bromodomains of BRD4, similar to JQ-1, but with a preference for BD2 over BD1. RVX-208 also binds to the bromodomains of BRDs 2 and 3 with a similar preference for BD2 (Kd~5–30 nM) over BD1 (Kd~2–3 uM). Treatment of humans for 1 week with oral RVX-208 increased apoA-I, pre-beta-HDL, and HDL functionality. Resverlogix Corp. has commenced a Phase 3 clinical trial in cardiovascular disease patients with type 2 diabetes mellitus with a primary endpoint of time to first occurrence of Major Adverse Cardiac Events (MACE).
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
360 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29854980 |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
APABETALONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2306 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29854980 |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
APABETALONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.97 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29854980 |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
APABETALONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
100 mg 2 times / day multiple, oral Studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Elevated liver enzyme levels... AEs leading to discontinuation/dose reduction: Elevated liver enzyme levels (2.9%) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Elevated liver enzyme levels | 2.9% Disc. AE |
100 mg 2 times / day multiple, oral Studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Data on gene and protein expression changes induced by apabetalone (RVX-208) in ex vivo treated human whole blood and primary hepatocytes. | 2016-09 |
|
| RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease. | 2016-04 |
|
| RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist. | 2013 |
|
| RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. | 2010-06-08 |
Patents
Sample Use Guides
Experimental doses of 50, 100 or 150 mg twice daily for 12 weeks, orally with meals in the morning and in the evening, 10 to 12 hours apart in patients with atherosclerosis and coronary artery disease.
Route of Administration:
Oral
| Substance Class |
Chemical
Created
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8R4A7GDZ1D
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TARGET->ACTIVATOR OF EXPRESSION |
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TARGET -> INHIBITOR |
Suppressed gene expression of VI mediators in monocytes and endothelial cells by inhibiting BET-dependent transcription induced by multiple inflammatory stimuli. In CVD patients, apabetalone treatment reduced circulating levels of VI mediators, an outcome conducive with atherosclerotic plaque stabilization and MACE reduction.
IC50
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ACTIVE MOIETY |
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