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| Targets |
IC50: 0.5 μM (PCSK9)[1]
The primary target of SBC-115337 is proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that regulates plasma cholesterol levels by promoting the degradation of the low-density lipoprotein receptor (LDLR). SBC-115337 is a potent inhibitor of PCSK9, with an IC50 value of 0.5 μM as determined in biochemical assays. By inhibiting PCSK9, the compound prevents the PCSK9-mediated degradation of LDLR, thereby increasing the number of LDLRs available on the cell surface to clear LDL-cholesterol from the circulation. This mechanism is distinct from statins and represents a key target for lipid-lowering therapies. |
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| ln Vitro |
To track the impact of PCSK9 binding to the recombinant LDLR, an in vitro ELISA test was used to detect the IC50 of the powerful drug (SBC-115,337), which is 0.6 μM. At 1.2 μM, SBC-115,337 causes a tenfold increase in LDLR expression in HepG2 cells compared to the control group. It also boosts the uptake of fluorescently tagged DiI-LDL and decreases LDL-c levels in mice that are fed a high-fat diet[2].
In vitro, SBC-115337 demonstrates potent inhibition of PCSK9. In an ELISA-based assay monitoring the binding of PCSK9 to recombinant LDLR, the compound exhibits an IC50 of 0.6 μM. Importantly, studies have shown that SBC-115337 does not affect the synthesis, processing, or secretion of PCSK9, indicating its mechanism of action is through direct inhibition of PCSK9 function rather than its production. In HepG2 cells, treatment with SBC-115337 at a concentration of 1.2 μM leads to a more than ten-fold increase in LDLR expression compared to the control group. This upregulation of LDLR is functional, as it increases the cellular uptake of fluorescently labeled DiI-LDL. |
| ln Vivo |
In vivo, SBC-115337 has been shown to lower LDL-cholesterol (LDL-c) levels in animal models. In high-fat diet-fed mice, the compound reduces LDL-c levels. This in vivo efficacy is consistent with its mechanism of action as a PCSK9 inhibitor, which leads to increased LDLR expression and enhanced clearance of LDL-cholesterol from the bloodstream. These findings support the potential of SBC-115337 as a research tool for studying the PCSK9 pathway and its role in lipid metabolism and cardiovascular disease.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for SBC-115337 typically involve monitoring the interaction between PCSK9 and the low-density lipoprotein receptor (LDLR). An ELISA-based assay is commonly used, where recombinant LDLR is immobilized, and PCSK9 is incubated with varying concentrations of the test compound. The amount of PCSK9 bound to LDLR is then detected using a specific antibody. The compound's ability to inhibit this interaction is quantified, and the IC50 value is determined from the concentration-response curve.
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| Cell Assay |
In vitro cellular assays for SBC-115337 are performed using cell lines such as HepG2 (human liver carcinoma cells). Cells are treated with the compound at various concentrations, and the expression of LDLR is measured. This can be done by analyzing cell lysates via Western blotting to quantify LDLR protein levels or by using fluorescently labeled LDL (DiI-LDL) to measure the functional uptake of LDL into the cells. These assays demonstrate that the compound's inhibition of PCSK9 translates to increased LDLR expression and activity in a cellular context.
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| Animal Protocol |
In vivo animal studies for SBC-115337 are typically conducted in mouse models, such as those fed a high-fat diet. The compound can be administered via oral gavage or intraperitoneal injection. Following treatment, blood samples are collected to measure plasma lipid levels, including LDL-cholesterol (LDL-c). The compound's ability to lower LDL-c levels is the primary endpoint for assessing its in vivo efficacy. These studies help to validate the PCSK9 inhibitory mechanism as a viable strategy for reducing cholesterol.
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| ADME/Pharmacokinetics |
SBC-115337 is a small molecule with a molecular weight of 473.48. It is supplied as a powder and is soluble in DMSO at 10 mg/mL (21.12 mM). It is typically stored as a powder at -20°C for up to 3 years or in solution at -80°C for up to 1 year. Detailed pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution are not available in the public domain, as the compound is primarily used as a research tool rather than a clinical candidate.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for SBC-115337 in the available literature. As a research chemical, it is intended for laboratory use only and should be handled with standard safety precautions. It is not approved for human therapeutic use. Researchers should consult the material safety data sheet (MSDS) for detailed safety and handling information.
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| References | |
| Additional Infomation |
SBC-115337 is a potent benzofuran compound that acts as an inhibitor of PCSK9, a key regulator of LDL-cholesterol metabolism. It has a molecular formula of C29H19N3O4 and a molecular weight of 473.48. The compound inhibits PCSK9 with an IC50 of 0.5 μM and, in HepG2 cells, increases LDLR expression more than ten-fold at 1.2 μM. It also lowers LDL-c levels in high-fat diet-fed mice. SBC-115337 is used as a research tool to study the PCSK9-LDLR axis in cholesterol metabolism and cardiovascular disease.
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| Molecular Formula |
C29H19N3O4
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| Molecular Weight |
473.478866815567
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| Exact Mass |
473.137
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| CAS # |
423148-46-3
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| PubChem CID |
1369939
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| Appearance |
Light yellow to brown solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
777
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(C(NC2C=CC(=CC=2)C(NC2C=CC(=CC=2)C2=NC3C=CC=CC=3O2)=O)=O)=CC2C=CC=CC1=2
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| InChi Key |
ALQIZRCPSILFNQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H19N3O4/c33-27(30-21-15-11-19(12-16-21)29-32-23-6-2-4-8-25(23)36-29)18-9-13-22(14-10-18)31-28(34)26-17-20-5-1-3-7-24(20)35-26/h1-17H,(H,30,33)(H,31,34)
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| Chemical Name |
N-[4-[[4-(1,3-benzoxazol-2-yl)phenyl]carbamoyl]phenyl]-1-benzofuran-2-carboxamide
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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: 6.67 mg/mL (14.09 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 | 2.1120 mL | 10.5601 mL | 21.1202 mL | |
| 5 mM | 0.4224 mL | 2.1120 mL | 4.2240 mL | |
| 10 mM | 0.2112 mL | 1.0560 mL | 2.1120 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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