AVASIMIBE

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

Structure Search

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)

HIDE SMILES / InChI

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acyl coenzyme A:cholesterol acyltransferase 1 15 Target ID: CHEMBL2782 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8978833 \| https://www.ncbi.nlm.nih.gov/pubmed/16820149	Inhibitor 8297	18.72 µM [IC50]
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15333513	Inhibitor 8297	2.9 µM [IC50]
Cytochrome P450 1A2 72 Target ID: CHEMBL3356 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15333513	Inhibitor 8297	13.9 µM [IC50]
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15333513	Inhibitor 8297	26.5 µM [IC50]
Acyl coenzyme A:cholesterol acyltransferase 2 4 Target ID: CHEMBL4465 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8978833 \| https://www.ncbi.nlm.nih.gov/pubmed/16820149	Inhibitor 8297	19.11 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atherosclerosis 74 Sources: http://adisinsight.springer.com/drugs/800008778	Primary		Phase III 656	Unknown Approved Use Unknown
Hyperlipidemia 80 Sources: http://adisinsight.springer.com/drugs/800008778	Primary		Phase III 656	Unknown Approved Use Unknown

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: https://pubmed.ncbi.nlm.nih.gov/11427213	unhealthy n = 26 Health Status: unhealthy Condition: hyperlipidemia Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11427213	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: https://pubmed.ncbi.nlm.nih.gov/11427213

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: https://pubmed.ncbi.nlm.nih.gov/11427213	unhealthy n = 26 Health Status: unhealthy Condition: hyperlipidemia Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11427213
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: https://pubmed.ncbi.nlm.nih.gov/11427213	unhealthy n = 26 Health Status: unhealthy Condition: hyperlipidemia Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11427213
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: https://pubmed.ncbi.nlm.nih.gov/11427213	unhealthy n = 26 Health Status: unhealthy Condition: hyperlipidemia Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11427213

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY106841	https://www.001chemical.com/chem/search?q=DY106841
1PlusChem LLC	1P001X8T	https://www.1pchem.com/search?query=1P001X8T
AChemBlock	10275	http://www.achemblock.com/catalogsearch/result/?q=10275
AK Scientific	V2056	https://aksci.com/item_detail.php?cat=V2056
ApexBio Technology	A4318	https://www.apexbt.com/catalogsearch/result/?q=A4318
AstaTech	C73212	http://astatechinc.com/CPSResult.php?CRNO=C73212
BOC Sciences	166518-60-1	http://www.bocsci.com/description.asp?cas=166518-60-1
Capot Chemical	22420	https://www.capotchem.com/search.do?q=22420
Cayman Chemical	18129	http://www.caymanchem.com/app/template/Product.vm/catalog/18129
Chem Scene	CS-5695	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5695
ChemShuttle	106830	https://www.chemshuttle.com/catalogsearch/result/?q=106830
Excenen	EX-A2230	http://www.excenen.com/searchresultlist.php?id=EX-A2230
Hairui	HR143003	http://www.hairuichem.com/en/product/search.do?q=HR143003
KeyOrganics	AS-74646	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74646
Matrix Scientific	132200	http://www.matrixscientific.com/132200.html
MedChem Express	HY-13215	https://www.medchemexpress.com/search.html?q=HY-13215&ft=&fa=&fp=
MolPort	MolPort-016-633-300	https://www.molport.com/shop/molecule-link/MolPort-016-633-300
Molcore	MC106841	http://www.molcore.com/CatMC106841.html
Molnova	M12538	https://www.molnova.com/en/serch-list.html?keywords=M12538
MuseChem	I002175	https://www.musechem.com/product/I002175.html
Ryan Scientific	Omeprazole_sulfide	https://ryansci.com/products?q=Omeprazole_sulfide&list_q=&search_type=exact
Selleck Chemicals	S2187	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2187
ShangHai Biochempartner	BCP000297	http://www.biochempartner.com/search_BCP000297
ShangHai Biochempartner	BCP02302	http://www.biochempartner.com/search_BCP02302
TargetMol	T2753	https://www.targetmol.com/search?keyword=T2753
Toronto Research Chemicals	A794680	https://www.trc-canada.com/product-detail/?CatNum=A794680
Toronto Research Chemicals	B693505	https://www.trc-canada.com/product-detail/?CatNum=B693505
eMolecules	32278227	https://orderbb.emolecules.com/search/#?query=32278227
eMolecules	95742435	https://orderbb.emolecules.com/search/#?query=95742435
eNovation Chemicals	D382125	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D382125&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-2481071538	https://mcule.com/MCULE-2481071538/

PubMed

Title	Date	PubMed
Avasimibe induces CYP3A4 and multiple drug resistance protein 1 gene expression through activation of the pregnane X receptor.	2003 Sep	12766253
Effects of avasimibe on cytochrome P450 2C9 expression in vitro and in vivo.	2004 Dec	15333513
Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction.	2006 Oct	16837568
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Regulation of cytochrome P450 2C9 expression in primary cultures of human hepatocytes.	2009 Jan-Feb	19202563

Patents

Sample Use Guides

In Vivo Use Guide

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

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.

Name

Type

Language

AVASIMIBE

Official Name

English

Avasimibe [WHO-DD]

Common Name

English

AVASIMIBE [MI]

Common Name

English

AVASIMIBE [USAN]

Common Name

English

CI-1011

Code

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