Pactimibe sulfate (CS-505) is an ACAT1/2 dual (bifunctional) inhibitor (antagonist) with IC50s of 4.9 μM for ACAT1 and 3.0 μM for ACAT2. Pactimibe sulfate (CS-505) inhibits ACAT with IC50s of 2.0 μM in hepatocytes, 2.7 μM in macrophages, and 4.7 μM in THP-1 cells. Pactimibe sulfate (CS-505) noncompetitively inhibits oleoyl-CoA with Ki of 5.6 μM. In addition, Pactimibe sulfate (CS-505) significantly inhibited the formation of cholesteryl esters with IC50 of 6.7 μM. Pactimibe sulfate (CS-505) has anti-atherosclerotic potential and has plasma cholesterol-lowering activity.

Physicochemical Properties

Molecular Formula	C25H40N2O3.1/2H2O4S
Molecular Weight	465.65
Exact Mass	930.575
CAS #	608510-47-0
Related CAS #	Pactimibe;189198-30-9
PubChem CID	11953348
Appearance	Off-white to gray solid powder
LogP	13.133
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	22
Heavy Atom Count	65
Complexity	653
Defined Atom Stereocenter Count	0
InChi Key	MKJQESRCXYYHFR-UHFFFAOYSA-N
InChi Code	InChI=1S/2C25H40N2O3.H2O4S/c2*1-7-8-9-10-11-12-14-27-15-13-19-17(2)20(16-21(28)29)18(3)22(23(19)27)26-24(30)25(4,5)6;1-5(2,3)4/h2*7-16H2,1-6H3,(H,26,30)(H,28,29);(H2,1,2,3,4)
Chemical Name	2-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-1-octyl-2,3-dihydroindol-5-yl]acetic acid;sulfuric acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	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)
ln Vitro	In monocyte-derived macrophages, pactimibe sulfate (CS-505) causes a mild ACAT inhibition, which suppresses the development of foam cells[2].
ln Vivo	Pactimibe sulfate (CS-505; oral gavage; 60 and 200 mg/kg/day; twice daily; 12 weeks) inhibits ACAT-1 and ACAT-2, which lowers plasma cholesterol but has no effect on areas that are collagen- or macrophage-positive[3].
Animal Protocol	Animal/Disease Models: Male C57BL/6J ApoE−/− mice aged 8weeks old[3] Doses: 60 and 200 mg/kg/day Route of Administration: Oral gavage; twice a day; 12 weeks Experimental Results: diminished plasma cholesterol levels by 39% and 74% at the administration of 60 and 200 mg/kg/day.
References	[1]. 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]. 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]. 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.

Solubility Data

Solubility (In Vitro)

DMSO: 120 mg/mL (257.70 mM) H2O: < 0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6 mg/mL (12.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6 mg/mL (12.89 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 6 mg/mL (12.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1475 mL	10.7377 mL	21.4754 mL
	5 mM	0.4295 mL	2.1475 mL	4.2951 mL
	10 mM	0.2148 mL	1.0738 mL	2.1475 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.