PACTIMIBE

Investigational

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 Search

SMILES

CCCCCCCCN1CCC2=C1C(NC(=O)C(C)(C)C)=C(C)C(CC(O)=O)=C2C

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16814766 | https://clinicaltrials.gov/ct2/show/NCT00185146 | https://clinicaltrials.gov/ct2/show/NCT00185042 | https://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/005079.html

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

PubMed

Title	Date	PubMed
A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice.	2010-11	20843517
Novel tetrahydroisoquinoline derivatives with inhibitory activities against acyl-CoA: cholesterol acyltransferase and lipid peroxidation.	2010-08	20686261
Novel acyl-CoA: cholesterol acyltransferase inhibitor: indoline-based sulfamide derivatives with low lipophilicity and protein binding ratio.	2010-08	20686260
Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study.	2010-06-14	20546600
Impact of medical therapy on atheroma volume measured by different cardiovascular imaging modalities.	2010	20672024
Novel indoline-based acyl-CoA: cholesterol acyltransferase inhibitor: Effects of introducing a methanesulfonamide group on physicochemical properties and biological activities.	2009-08-15	19608421
Carotid atherosclerosis progression and ACAT inhibition.	2009-07-15	19602681
Atherosclerosis drug fails to meet Phase III trial end point.	2009-05	19404306
ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial.	2009-03-18	19293413
Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and implications in drug development.	2009	19601803
Effect of CYP2D6 polymorphism on pharmacokinetics of a novel ACAT inhibitor, pactimibe and its unique metabolite, R-125528.	2008-11	19000552
Forkhead transcription factors (FoxOs) promote apoptosis of insulin-resistant macrophages during cholesterol-induced endoplasmic reticulum stress.	2008-11	18728232
Novel binding mode of the acidic CYP2D6 substrates pactimibe and its metabolite R-125528.	2008-09	18524873
Effects of ketoconazole and quinidine on pharmacokinetics of pactimibe and its plasma metabolite, R-125528, in humans.	2008-08	18448569
CYP2D6-Mediated metabolism of a novel acyl coenzyme A:cholesterol acyltransferase inhibitor, pactimibe, and its unique plasma metabolite, R-125528.	2008-03	18056254
ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice.	2007-02	16626720
[New agents against atherosclerosis tested. Alarming findings, ACAT inhibitors seem to have proatherogenic effects].	2006-11-23	17117657
Multiple mechanisms of hypocholesterolemic action of pactimibe, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor.	2006-08-14	16814766
Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe.	2006-07-01	16730694
Intravascular ultrasound assessment of novel antiatherosclerotic therapies: rationale and design of the Acyl-CoA:Cholesterol Acyltransferase Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Study.	2006-07	16824833
ACAT inhibition and the progression of coronary atherosclerosis.	2006-06-15	16775245
Pactimibe stabilizes atherosclerotic plaque through macrophage acyl-CoA:cholesterol acyltransferase inhibition in WHHL rabbits.	2006-06-06	16690054
Failure of ACAT inhibition to retard atherosclerosis.	2006-03-23	16554534
Effect of ACAT inhibition on the progression of coronary atherosclerosis.	2006-03-23	16554527
A bumpy road to breakthroughs. The news: it's hard to beat today's cardiac treatments.	2006-02	17763560

Patents

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:29:17 GMT 2025` Edited by `admin` on `Mon Mar 31 18:29:17 GMT 2025`
Record UNII	D874R9PZ9T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PACTIMIBE

Official Name

English

Pactimibe [WHO-DD]

Preferred 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