U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C29H43NO4S
Molecular Weight 501.7232
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVASIMIBE

SMILES

CC(C)c1cc(C(C)C)c(CC(=NS(=O)(=O)Oc2c(cccc2C(C)C)C(C)C)O)c(c1)C(C)C

InChI

InChIKey=PTQXTEKSNBVPQJ-UHFFFAOYSA-N
InChI=1S/C29H43NO4S/c1-17(2)22-14-25(20(7)8)27(26(15-22)21(9)10)16-28(31)30-35(32,33)34-29-23(18(3)4)12-11-13-24(29)19(5)6/h11-15,17-21H,16H2,1-10H3,(H,30,31)

HIDE SMILES / InChI

Molecular Formula C29H43NO4S
Molecular Weight 501.7232
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8978833 | https://www.ncbi.nlm.nih.gov/pubmed/16820149

Avasimibe (CI 1011) is a potent ACAT (Acyl-CoA:cholesterol acyltransferase) inhibitor. Avasimibe inhibits both ACAT1 and ACAT2 isoforms. Avasimibe was in development by Parke-Davis (now Pfizer) in the US for the treatment of atherosclerosis and hyperlipidaemia. Avasimibe was in phase III studies and more than 1300 patients had been treated for up to one year, however, in October 2003, Pfizer announced that development had been discontinued.

CNS Activity

Curator's Comment:: Avasimibe (CI 1011) had reduced ACAT-mediated generation of cholesteryl esters in the mouse brain, however little is known about blood-brain barrier penetrability of CI-1011. No human data available.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
500 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy
n = 26
Health Status: unhealthy
Condition: hyperlipidemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 26
Sources:
Disc. AE: Constipation...
Other AEs: Myasthenia, Headache...
AEs leading to
discontinuation/dose reduction:
Constipation (1 pt)
Other AEs:
Myasthenia (3.8%)
Headache (3.8%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Constipation 1 pt
Disc. AE
500 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy
n = 26
Health Status: unhealthy
Condition: hyperlipidemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 26
Sources:
Headache 3.8%
500 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy
n = 26
Health Status: unhealthy
Condition: hyperlipidemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 26
Sources:
Myasthenia 3.8%
500 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy
n = 26
Health Status: unhealthy
Condition: hyperlipidemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 26
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Avasimibe induces CYP3A4 and multiple drug resistance protein 1 gene expression through activation of the pregnane X receptor.
2003 Sep
Effects of avasimibe on cytochrome P450 2C9 expression in vitro and in vivo.
2004 Dec
Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction.
2006 Oct
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Regulation of cytochrome P450 2C9 expression in primary cultures of human hepatocytes.
2009 Jan-Feb
Patents

Patents

Sample Use Guides

Following an 8-week placebo and dietary-controlled baseline period, patients with combined hyperlipidemia and hypoalphalipoproteinemia were randomly assigned to double-blind treatment with placebo, 50, 125, 250, or 500 mg Avasimibe (CI 1011) administered as capsules once daily for 8 weeks. At all evaluated doses, avasimibe treatment resulted in prompt and significant reductions in plasma levels of total triglycerides and very low-density lipoprotein cholesterol, apparently independent of dose. All doses of avasimibe were well tolerated with no resulting significant abnormalities of biochemical, hematological, or clinical parameters.
Route of Administration: Oral
1-10 ug/ml Avasimibe (CI 1011) exerted anti-atherogenic effects by reducing TC accumulation, inhibiting acLDL binding, and by limiting lipid storage in cultured primary human macrophages.
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:28:15 UTC 2021
Edited
by admin
on Sat Jun 26 05:28:15 UTC 2021
Record UNII
28LQ20T5RC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AVASIMIBE
INN   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
AVASIMIBE [MI]
Common Name English
AVASIMIBE [USAN]
Common Name English
CI-1011
Code English
AVASIMIBE [WHO-DD]
Common Name English
AVASIMIBE [INN]
Common Name English
N-((2,6-BIS(1-METHYLETHYL)PHENOXY)SULFONYL)-2,4,6-TRIS(1-METHYLETHYL)-BENZENEACETAMIDE
Systematic Name English
2,6-BIS(1-METHYLETHYL)PHENYL ((2,4,6-TRIS(1-METHYLETHYL)PHENYL)ACETYL)SULFAMATE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C29703
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
Code System Code Type Description
DRUG BANK
DB06442
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL101309
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
INN
7792
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
MERCK INDEX
M2146
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY Merck Index
FDA UNII
28LQ20T5RC
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
EPA CompTox
166518-60-1
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
CAS
166518-60-1
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
NCI_THESAURUS
C75252
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
EVMPD
SUB00632MIG
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
PUBCHEM
166558
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
MESH
C423185
Created by admin on Sat Jun 26 05:28:15 UTC 2021 , Edited by admin on Sat Jun 26 05:28:15 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INDUCER
Related Record Type Details
ACTIVE MOIETY