| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| 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)
ACAT1 (IC50: 4.9 uM) and ACAT2 (IC50: 3.0 uM) |
|---|---|
| ln Vitro |
In monocyte-derived macrophages, pactimibe sulfate (CS-505) causes a mild ACAT inhibition, which suppresses the development of foam cells[2].
Pactimibe sulfate inhibits ACAT with IC50 values of 2.0 uM in hepatocytes, 2.7 uM in macrophages, and 4.7 uM in THP-1 cells. It induces moderate ACAT inhibition in monocyte-derived macrophages, leading to suppression of foam cell formation. In vitro metabolic studies show pactimibe has two dominant clearance pathways: formation of R-125528 by CYP3A4 and M-1 by CYP2D6, along with omega-1 oxidation, N-dealkylation, and glucuronidation. |
| 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].
In atherogenic diet-fed hamsters, pactimibe (3 and 10 mg/kg for 90 days) decreases serum total cholesterol by 70% and 72% and aortic fatty streak area by 79% and 95%, respectively. It exerts potent lipid-lowering and anti-atherosclerotic effects. It has been investigated in humans for the treatment of hypercholesterolemia and atherosclerotic diseases. |
| Enzyme Assay |
Dual ACAT1/2 inhibition assay: recombinant human ACAT1 and ACAT2 are expressed in insect cells, and microsomes are prepared. Enzyme activity is measured using [14C]-oleoyl-CoA as the acyl donor and cholesterol as acceptor. Reactions are incubated at 37degC for 10-30 minutes, stopped by organic extraction, and the product (cholesteryl oleate) is separated by TLC and quantified by scintillation counting. IC50 values are 4.9 uM (ACAT1) and 3.0 uM (ACAT2). Primary human hepatocytes, macrophages (derived from THP-1 cells or human monocytes), and THP-1 cells are cultured in appropriate media. Cells are treated with pactimibe sulfate (0.1-50 uM) for 24-48 hours in the presence of acetylated LDL (acLDL, 50 ug/mL) to induce foam cell formation. Cellular cholesteryl ester content is measured by enzymatic colorimetric kits after lipid extraction. Foam cell formation is quantified by Oil Red O staining and microscopy.
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| 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. Male Syrian golden hamsters are fed an atherogenic diet (high cholesterol and fat) for 4-8 weeks to induce hypercholesterolemia and aortic fatty streak formation. Pactimibe sulfate is formulated in a suitable vehicle (e.g., 0.5% methylcellulose) and administered orally (gavage) once daily at doses of 1-30 mg/kg for 4-12 weeks. Endpoints include serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (enzymatic assays), and aortic fatty streak area (en face Oil Red O staining). Histopathological evaluation of the aorta and liver is performed. |
| ADME/Pharmacokinetics |
Pactimibe sulfate is orally bioavailable. In humans, it is metabolized by CYP3A4 and CYP2D6 to form active metabolites, including R-125528. Pharmacokinetic studies have been conducted in humans: the compound shows absorption with peak plasma concentrations achieved within 2-4 hours post-dose. Half-life is approximately 6-12 hours. Metabolism involves omega-1 oxidation, N-dealkylation, and glucuronidation. Excretion is primarily via bile and urine. Drug-drug interaction potential exists with CYP3A4 and CYP2D6 inhibitors.
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| Toxicity/Toxicokinetics |
Pactimibe sulfate has been evaluated in clinical trials and has an established safety profile. Adverse effects reported in clinical studies include mild-to-moderate gastrointestinal disturbances (diarrhea, nausea, abdominal pain), and reversible elevations in liver transaminases (ALT, AST). No significant genotoxicity, cardiotoxicity, or target organ toxicity was reported at therapeutic doses. However, development was discontinued, possibly due to efficacy or safety concerns.
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| References |
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| Additional Infomation |
Pactimibe sulfate (CS-505) was developed as a dual ACAT1/2 inhibitor for hypercholesterolemia and atherosclerosis. It advanced to clinical trials but development was discontinued. The compound is a research tool for studying ACAT inhibition, cholesterol metabolism, and atherosclerosis. It is not approved for clinical use. Molecular formula: (C25H38N2O3)2·H2SO4. It is soluble in DMSO. A patent covering pactimibe was filed in the early 2000s. The compound has been investigated for its anti-atherosclerotic potency and dual ACAT1/2 inhibition mechanism.
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| Molecular Formula |
C25H40N2O3.1/2H2O4S
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|---|---|
| Molecular Weight |
465.65
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| Exact Mass |
930.575
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| CAS # |
608510-47-0
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| Related CAS # |
Pactimibe;189198-30-9
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| PubChem CID |
11953348
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| Appearance |
Off-white to gray solid powder
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| LogP |
13.133
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
65
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| Complexity |
653
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCCCN1CCC2=C(C(=C(C(=C21)NC(=O)C(C)(C)C)C)CC(=O)O)C.CCCCCCCCN1CCC2=C(C(=C(C(=C21)NC(=O)C(C)(C)C)C)CC(=O)O)C.OS(=O)(=O)O
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| InChi Key |
MKJQESRCXYYHFR-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-1-octyl-2,3-dihydroindol-5-yl]acetic acid;sulfuric acid
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 120 mg/mL (257.70 mM)
H2O: < 0.1 mg/mL |
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT00151788
Conditions:Atherosclerosis|Heterozygous Familial HypercholesterolemiaProducts are for research use only; We do not sell to patients
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