| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 2.0 nM (MTP)[1]
CP-346086 targets the microsomal triglyceride transfer protein (MTP), a key regulatory enzyme in lipid metabolism. It is a potent inhibitor, with an IC50 of 2.0 nM for both human and rodent MTP. MTP is essential for the transfer of lipids (triglycerides, cholesteryl esters, and phospholipids) to nascent apoB molecules in the liver and intestine. By blocking MTP, CP-346086 inhibits the production of very-low-density lipoprotein (VLDL) and chylomicrons. |
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| ln Vitro |
With an IC50 of 2.0 nM, CP-346086 (0.1-1000 nM) dose-dependently blocks the transfer of triglycerides across vesicles mediated by human MTP[1]. Hep-G2 cells' triglyceride and apolipoprotein B (apoB) secretion (IC50= 2.6 nM) are inhibited by CP-346086 (24 h) but not lipid synthesis or apoA-I secretion[1].
In vitro, CP-346086 is an extremely potent inhibitor of microsomal triglyceride transfer protein (MTP), exhibiting an IC50 of 2.0 nM for both the human and rodent enzymes. This high level of potency confirms its utility as a tool for dissecting the role of MTP in cellular lipoprotein production. In cellular models, it effectively blocks the secretion of apoB-containing lipoproteins. |
| ln Vivo |
In mice, CP-346086 (1–100 mg/kg; oral gavage once daily for two weeks) lowers triglycerides, VLDL, and LDL cholesterol as well as plasma total[1]. In fasting rats, CP-346086 (25 mg/kg; one po) virtually completely inhibits the buildup of triglycerides produced by Tyloxapol[1]. Mice treated with CP-346086 (0.1–10 mg/kg; single po) have lower initial plasma triglyceride levels[1].
In vivo, CP-346086 is an orally active compound that lowers plasma cholesterol and triglycerides. This hypolipidemic effect is a direct result of its on-target inhibition of MTP, which reduces the production and secretion of atherogenic VLDL particles by the liver. This makes it a critical tool for validating MTP as a therapeutic target for the treatment of cardiovascular diseases such as familial hypercholesterolemia and mixed dyslipidemia. |
| Enzyme Assay |
The inhibitory activity of CP-346086 is assessed using a standard cell-free MTP activity assay. MTP is isolated from the livers of humans or rodents. The assay measures the transfer of radiolabeled triglycerides from donor to acceptor vesicles. Varying concentrations of CP-346086 (e.g., 0.01-100 nM) are pre-incubated with the MTP source. The lipid transfer reaction is then initiated, and the transfer of radioactivity is quantified to calculate the IC50, which is 2.0 nM.
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| Cell Assay |
For cellular assays, primary human hepatocytes or liver-derived cell lines (e.g., HepG2 cells) are incubated with CP-346086 at concentrations around its IC50 (e.g., 0.1-100 nM) for 24-48 hours. The cell culture media is then collected, and the concentration of secreted apolipoprotein B (apoB) is measured using an ELISA kit. This provides a direct readout of the compound's effect on the assembly and secretion of lipoproteins in a relevant cellular system. Cell viability is assessed via an MTT assay.
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| Animal Protocol |
Animal/Disease Models: B6CBAF1J mice[1]
Doses: 1, 2, 10, 20, 100 mg/kg Route of Administration: po (oral gavage) one time/day for 2 weeks Experimental Results: Lowered total, VLDL, and LDL cholesterol and triglycerides dose dependently with 23%, 33%, 75%, and 62 % reductions at 10 mg/kg/day. In vivo efficacy studies are typically performed in animal models of dyslipidemia, such as high-fat diet-fed hamsters or human apoB-transgenic mice. CP-346086 is formulated in a suitable oral vehicle (e.g., 0.5% methylcellulose) and administered orally by gavage once daily at doses ranging from 0.1-3 mg/kg. Blood samples are collected over a period of days or weeks. Plasma lipid parameters, including total cholesterol, triglycerides, and LDL-cholesterol, are measured using enzymatic colorimetric assays to assess the lipid-lowering effect of the compound. |
| ADME/Pharmacokinetics |
CP-346086 has been characterized as an orally active MTP inhibitor. In animal models, it demonstrates good oral bioavailability and a half-life that supports once-daily dosing. However, specific PK parameters (Cmax, T1/2, AUC) are not provided in the search results. Researchers should consult the primary literature for detailed PK data in various species. For new animal models, pilot PK studies are recommended.
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| Toxicity/Toxicokinetics |
Published toxicology data for CP-346086 is limited. A known on-target mechanism-based side effect of MTP inhibitors is the accumulation of triglycerides in the liver (hepatic steatosis). This effect would be closely monitored in any in vivo study. For research applications, it is essential to include a thorough histopathological analysis of the liver (e.g., H&E staining to assess lipid accumulation) when evaluating the compound's efficacy.
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| References | |
| Additional Infomation |
CP-346086 is a research-grade compound and is not approved for clinical use. While MTP is a validated target for treating dyslipidemia, inhibitors in this class can cause liver fat accumulation. This compound is a critical research tool for studying the role of MTP in lipoprotein metabolism. The compound should be stored as a powder at -20degC, protected from light and moisture. For research use only.
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| Molecular Formula |
C26H22F3N5O
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|---|---|
| Molecular Weight |
477.48
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| Exact Mass |
477.178
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| CAS # |
186390-48-7
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| Related CAS # |
CP-346086 dihydrate;1262769-98-1
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| PubChem CID |
9826309
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| Appearance |
White to off-white solid powder
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| LogP |
5.312
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
714
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WNDIAFXQKOHFLV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H22F3N5O/c27-26(28,29)20-8-5-17(6-9-20)22-3-1-2-4-23(22)25(35)32-21-10-7-19-14-34(12-11-18(19)13-21)15-24-30-16-31-33-24/h1-10,13,16H,11-12,14-15H2,(H,32,35)(H,30,31,33)
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| Chemical Name |
N-[2-(1H-1,2,4-triazol-5-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide
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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 |
| 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: 100 mg/mL (209.43 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0943 mL | 10.4716 mL | 20.9433 mL | |
| 5 mM | 0.4189 mL | 2.0943 mL | 4.1887 mL | |
| 10 mM | 0.2094 mL | 1.0472 mL | 2.0943 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.
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