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Details

Stereochemistry ACHIRAL
Molecular Formula C25H40N2O3
Molecular Weight 416.5967
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PACTIMIBE

SMILES

CCCCCCCCN1CCC2=C(C)C(CC(O)=O)=C(C)C(NC(=O)C(C)(C)C)=C12

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 416.5967
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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.

Originator

Approval Year

Unknown
139594
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
Intravascular ultrasound assessment of novel antiatherosclerotic therapies: rationale and design of the Acyl-CoA:Cholesterol Acyltransferase Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Study.
2006 Jul
Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe.
2006 Jul 1
ACAT inhibition and the progression of coronary atherosclerosis.
2006 Jun 15
Pactimibe stabilizes atherosclerotic plaque through macrophage acyl-CoA:cholesterol acyltransferase inhibition in WHHL rabbits.
2006 Jun 6
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
CYP2D6-Mediated metabolism of a novel acyl coenzyme A:cholesterol acyltransferase inhibitor, pactimibe, and its unique plasma metabolite, R-125528.
2008 Mar
Effect of CYP2D6 polymorphism on pharmacokinetics of a novel ACAT inhibitor, pactimibe and its unique metabolite, R-125528.
2008 Nov
Forkhead transcription factors (FoxOs) promote apoptosis of insulin-resistant macrophages during cholesterol-induced endoplasmic reticulum stress.
2008 Nov
Novel binding mode of the acidic CYP2D6 substrates pactimibe and its metabolite R-125528.
2008 Sep
Novel indoline-based acyl-CoA: cholesterol acyltransferase inhibitor: Effects of introducing a methanesulfonamide group on physicochemical properties and biological activities.
2009 Aug 15
Atherosclerosis drug fails to meet Phase III trial end point.
2009 May
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
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

Patents

06063806
1
06200988
2
JP2002145774A
1
JP2005263788A
1
JP2007051085A
1
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:29:10 UTC 2023
Edited
by admin
on Fri Dec 15 16:29:10 UTC 2023
Record UNII
D874R9PZ9T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PACTIMIBE
INN   WHO-DD  
INN  
Official Name English
Pactimibe [WHO-DD]
Common Name English
(7-(2,2-DIMETHYLPROPANAMIDO)-4,6-DIMETHYL-1-OCTYLINDOLIN-5-YL)ACETIC ACID
Systematic Name English
pactimibe [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C471
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
Code System Code Type Description
DRUG BANK
DB12971
Created by admin on Fri Dec 15 16:29:10 UTC 2023 , Edited by admin on Fri Dec 15 16:29:10 UTC 2023
PRIMARY
NCI_THESAURUS
C66290
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
PRIMARY
FDA UNII
D874R9PZ9T
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
PRIMARY
EPA CompTox
DTXSID80172315
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
PRIMARY
INN
8269
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
PRIMARY
SMS_ID
300000036933
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
PRIMARY
MESH
C509302
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
PRIMARY
CAS
189198-30-9
Created by admin on Fri Dec 15 16:29:10 UTC 2023 , Edited by admin on Fri Dec 15 16:29:10 UTC 2023
PRIMARY
PUBCHEM
3081927
Created by admin on Fri Dec 15 16:29:11 UTC 2023 , Edited by admin on Fri Dec 15 16:29:11 UTC 2023
PRIMARY
ChEMBL
CHEMBL478858
Created by admin on Fri Dec 15 16:29:10 UTC 2023 , Edited by admin on Fri Dec 15 16:29:10 UTC 2023
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Structure of PACTIMIBE SULFATE
SALT/SOLVATE -> PARENT
Sterol O-acyltransferase 1
TARGET -> INHIBITOR
LIVER CARBOXYLESTERASE 1
TARGET -> INHIBITOR
CYTOCHROME P450 2D6
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
Structure of 7-((2,2-DIMETHYL-1-OXOPROPYL)AMINO)-1-(7-HYDROXYOCTYL)-4,6-DIMETHYL-1H-INDOLE-5-ACETIC ACID
METABOLITE -> PARENT
Structure of 1H-INDOLE-5-ACETIC ACID, 7-((2,2-DIMETHYL-1-OXOPROPYL)AMINO)-4,6-DIMETHYL-1-OCTYL-
METABOLITE -> PARENT
Structure of 1H-INDOLE-5-ACETIC ACID, 7-((2,2-DIMETHYL-1-OXOPROPYL)AMINO)-2,3-DIHYDRO-1-(7-HYDROXYOCTYL)-4,6-DIMETHYL-
METABOLITE -> PARENT
Related Record Type Details
Structure of PACTIMIBE
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

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