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Details

Stereochemistry ACHIRAL
Molecular Formula C25H40N2O3
Molecular Weight 416.5976
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PACTIMIBE

SMILES

CCCCCCCCN1CCc2c(C)c(CC(=O)O)c(C)c(c21)N=C(C(C)(C)C)O

InChI

InChIKey=TXIIZHHIOHVWJD-UHFFFAOYSA-N
InChI=1S/C25H40N2O3/c1-7-8-9-10-11-12-14-27-15-13-19-17(2)20(16-21(28)29)18(3)22(23(19)27)26-24(30)25(4,5)6/h7-16H2,1-6H3,(H,26,30)(H,28,29)

HIDE SMILES / InChI

Molecular Formula C25H40N2O3
Molecular Weight 416.5976
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Daiichi Sankyo developed an inhibitor of acyl-coenzyme A:cholesterol acyltransferases (ACAT1 and ACAT2), pactimibe (also known as CS 505). Pactimibe has been used in trials phase II for reducing the progression of coronary artery disease and in patients with atherosclerosis. However, on October 26, 2005, the company made the decision to discontinue all ongoing clinical studies of pactimibe, because of the secondary endpoints that showed a lower effect of the drug on atherosclerosis than the standard of care alone and no beneficial effect on the frequency of cardiovascular events.

Approval Year

PubMed

PubMed

TitleDatePubMed
Multiple mechanisms of hypocholesterolemic action of pactimibe, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor.
2006 Aug 14
A bumpy road to breakthroughs. The news: it's hard to beat today's cardiac treatments.
2006 Feb
ACAT inhibition and the progression of coronary atherosclerosis.
2006 Jun 15
Failure of ACAT inhibition to retard atherosclerosis.
2006 Mar 23
Effect of ACAT inhibition on the progression of coronary atherosclerosis.
2006 Mar 23
[New agents against atherosclerosis tested. Alarming findings, ACAT inhibitors seem to have proatherogenic effects].
2006 Oct 25-31
ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice.
2007 Feb
Effects of ketoconazole and quinidine on pharmacokinetics of pactimibe and its plasma metabolite, R-125528, in humans.
2008 Aug
Novel binding mode of the acidic CYP2D6 substrates pactimibe and its metabolite R-125528.
2008 Sep
Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and implications in drug development.
2009
Novel indoline-based acyl-CoA: cholesterol acyltransferase inhibitor: Effects of introducing a methanesulfonamide group on physicochemical properties and biological activities.
2009 Aug 15
Carotid atherosclerosis progression and ACAT inhibition.
2009 Jul 15
Impact of medical therapy on atheroma volume measured by different cardiovascular imaging modalities.
2010
Novel tetrahydroisoquinoline derivatives with inhibitory activities against acyl-CoA: cholesterol acyltransferase and lipid peroxidation.
2010 Aug
Novel acyl-CoA: cholesterol acyltransferase inhibitor: indoline-based sulfamide derivatives with low lipophilicity and protein binding ratio.
2010 Aug
Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study.
2010 Jun 14
A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice.
2010 Nov
Patents
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:46:30 UTC 2021
Edited
by admin
on Sat Jun 26 02:46:30 UTC 2021
Record UNII
D874R9PZ9T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PACTIMIBE
INN   WHO-DD  
INN  
Official Name English
(7-(2,2-DIMETHYLPROPANAMIDO)-4,6-DIMETHYL-1-OCTYLINDOLIN-5-YL)ACETIC ACID
Systematic Name English
PACTIMIBE [INN]
Common Name English
PACTIMIBE [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C471
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
Code System Code Type Description
DRUG BANK
DB12971
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
NCI_THESAURUS
C66290
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
FDA UNII
D874R9PZ9T
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
EPA CompTox
189198-30-9
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
INN
8269
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
MESH
C509302
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
CAS
189198-30-9
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
PUBCHEM
3081927
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
ChEMBL
CHEMBL478858
Created by admin on Sat Jun 26 02:46:30 UTC 2021 , Edited by admin on Sat Jun 26 02:46:30 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC IN HEALTHY MALE VOLUNTEERS

DOSE

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

IN HEALTHY MALE VOLUNTEERS

DOSE

Tmax PHARMACOKINETIC DOSE

IN HEALTHY MALE VOLUNTEERS

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC DOSE

ORAL ADMINISTRATION

IN HEALTHY MALE VOLUNTEERS