Details
Stereochemistry | ACHIRAL |
Molecular Formula | C29H43NO4S |
Molecular Weight | 501.721 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C1=CC(C(C)C)=C(CC(=O)NS(=O)(=O)OC2=C(C=CC=C2C(C)C)C(C)C)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)
Molecular Formula | C29H43NO4S |
Molecular Weight | 501.721 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: http://adisinsight.springer.com/drugs/800008778Curator'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
Sources: http://adisinsight.springer.com/drugs/800008778
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20613640
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2782 |
18.72 µM [IC50] | ||
Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15333513 |
2.9 µM [IC50] | ||
Target ID: CHEMBL3356 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15333513 |
13.9 µM [IC50] | ||
Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15333513 |
26.5 µM [IC50] | ||
Target ID: CHEMBL4465 |
19.11 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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%) Sources: Headache (3.8%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
PubMed
Title | Date | PubMed |
---|---|---|
Avasimibe induces CYP3A4 and multiple drug resistance protein 1 gene expression through activation of the pregnane X receptor. | 2003 Sep |
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Effects of avasimibe on cytochrome P450 2C9 expression in vitro and in vivo. | 2004 Dec |
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Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. | 2006 Oct |
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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
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11427213
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11882316
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
Edited
Fri Dec 15 15:26:49 GMT 2023
by
admin
on
Fri Dec 15 15:26:49 GMT 2023
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Record UNII |
28LQ20T5RC
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C29703
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FDA ORPHAN DRUG |
938123
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DB06442
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KK-05
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CHEMBL101309
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7792
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m2146
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28LQ20T5RC
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DTXSID80168117
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166518-60-1
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100000085327
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C75252
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SUB00632MIG
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166558
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C423185
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
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TRANSPORTER -> INDUCER |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
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