189198-30-9

189198-30-9 structure

Name: Pactimibe
Chemical Name: 2-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-1-octyl-2,3-dihydroindol-5-yl]acetic acid
CAS Number: 189198-30-9
Molecular Formula: C₂₅H₄₀N₂O₃
Molecular Weight: 416.59700
Catalog: Research Areas Cardiovascular Disease
Create Date: 2018-04-26 08:00:00
Modify Date: 2024-01-10 15:40:20
Pactimibe (CS-505 free base) is a dual ACAT1/2 inhibitor with IC50s of 4.9 μM and 3.0 μM, respectively. Pactimibe (CS-505 free base) inhibits ACAT with IC50s of 2.0 μM, 2.7 μM, 4.7 μM in the liver, macrophages and THP-1 cells, respectively[1]. Pactimibe (CS-505 free base) noncompetitively inhibits oleoyl-CoA with a Ki value of 5.6 μM. Moreover, Pactimibe (CS-505 free base) obviously inhibits cholesteryl ester formation with an IC50 of 6.7 μM. Pactimibe (CS-505 free base) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity[2].

Name	2-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-1-octyl-2,3-dihydroindol-5-yl]acetic acid
Synonyms	UNII-D874R9PZ9T Pactimibe

Description	Pactimibe (CS-505 free base) is a dual ACAT1/2 inhibitor with IC50s of 4.9 μM and 3.0 μM, respectively. Pactimibe (CS-505 free base) inhibits ACAT with IC50s of 2.0 μM, 2.7 μM, 4.7 μM in the liver, macrophages and THP-1 cells, respectively[1]. Pactimibe (CS-505 free base) noncompetitively inhibits oleoyl-CoA with a Ki value of 5.6 μM. Moreover, Pactimibe (CS-505 free base) obviously inhibits cholesteryl ester formation with an IC50 of 6.7 μM. Pactimibe (CS-505 free base) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity[2].
Related Catalog	Research Areas >> Cardiovascular Disease
Target	ACAT1:4.9 μM (IC50) ACAT2:3.0 μM (IC50) ACAT:2 μM (IC50, in the liver) ACAT:2.7 μM (IC50, in macrophages) ACAT:4.7 μM (IC50, in THP-1 cells) oleoyl-CoA:5.6 μM (Ki) cholesteryl ester formation:6.7 μM (IC50)
In Vitro	Pactimibe (CS-505 free base) induces moderate ACAT inhibition in monocyte-derived macrophages, leading to the suppression of foam cell formation[2].
In Vivo	Pactimibe (CS-505 free base; 60 and 200 mg/kg/day; oral gavage; twice a day; 12 weeks) induces an inhibition for ACAT-1 and ACAT-2, causing a reduction of plasma cholesterol but no influence on macrophage- or collagen-positive areas[3]. Animal Model: Male C57BL/6J ApoE−/− mice aged 8-week-old[3] Dosage: 60 and 200 mg/kg/day Administration: Oral gavage; twice a day; 12 weeks Result: Decreased plasma cholesterol levels by 39% and 74% at the administration of 60 and 200 mg/kg/day
References	[1]. Naoki Terasaka, et al. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Atherosclerosis. 2007 Feb;190(2):239-47. [2]. Ken Kitayama, et al. Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe. Eur J Pharmacol. 2006 Jul 1;540(1-3):121-30. [3]. Yasunobu Yoshinaka, et al. A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice. Atherosclerosis. 2010 Nov;213(1):85-91.

Density	1.071
Boiling Point	604.4ºC at 760 mmHg
Molecular Formula	C₂₅H₄₀N₂O₃
Molecular Weight	416.59700
Flash Point	319.3ºC
Exact Mass	416.30400
PSA	69.64000
LogP	5.77610
Vapour Pressure	1.86E-15mmHg at 25°C
Index of Refraction	1.547

189198-29-6

189198-30-9

Literature: Kyoto Pharmaceutical Industries, Ltd. Patent: US6063806 A1, 2000 ;

189199-92-6

111-83-1

189198-30-9

Literature: Sankyo Company, Limited Patent: EP1364942 A1, 2003 ; Location in patent: Page/Page column 25 ;

396653-57-9

189198-30-9

Literature: Takahashi, Kenji; Kasai, Masayasu; Ohta, Masaru; Shoji, Yoshimichi; Kunishiro, Kazuyoshi; Kanda, Mamoru; Kurahashi, Kazuyoshi; Shirahase, Hiroaki Journal of Medicinal Chemistry, 2008 , vol. 51, # 15 p. 4823 - 4833

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