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Purity: ≥98%
SBC-110736 (SBC110736) is a novel and potent small molecule inhibitor of proprotein convertase subtilisin kexin type 9 (PCSK9) with anti-hyperlipidemic effects. It has been reported to be able to lower cholesterol levels in mice. PCSK9 plays a major regulatory role in cholesterol homeostasis, mainly by reducing LDLR levels on the plasma membrane. Several studies have determined the potential use of PCSK9 inhibitors in the treatment of hyperlipoproteinemia (commonly called hypercholesterolemia). Furthermore, loss-of-function mutations in the PCSK9 gene result in lower levels of LDL and protection against cardiovascular disease.
| Targets |
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) [1]
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|---|---|
| ln Vitro |
Blocked the interaction between human PCSK9 protein and low-density lipoprotein receptor (LDLR): SBC-110736 competitively bound to PCSK9, preventing the formation of PCSK9-LDLR complexes in a concentration-dependent manner [1]
- Enhanced LDL uptake in hepatocytes: Treatment with SBC-110736 increased the uptake of fluorescently labeled LDL by human hepatoma cells, which was associated with elevated surface expression of LDLR [1] - Inhibited PCSK9-mediated LDLR degradation: SBC-110736 reduced the internalization and lysosomal degradation of LDLR induced by recombinant PCSK9, as demonstrated by immunoblot analysis of cell lysates [1] |
| ln Vivo |
Male C57BL/6 mice, SBC-110736, lower cholesterol in mice given a high-fat diet. Two weeks later, average total cholesterol levels were 38% lower than those of animals fed a high-fat diet, and lower than those of animals fed a high-fat diet. Normal levels of dietary cholesterol are restored by an average reduction of 50% [1].
Reduced plasma LDL-cholesterol (LDL-C) levels in hypercholesterolemic animal models: Administration of SBC-110736 led to a dose-dependent decrease in serum LDL-C concentrations, with significant reductions observed compared to vehicle-treated controls [1] - Increased hepatic LDLR expression: Post-treatment liver tissue analysis showed upregulated LDLR protein levels in animals administered SBC-110736, consistent with the in vitro mechanism of action [1] - Improved lipid profile: SBC-110736 also modestly reduced total cholesterol (TC) and apolipoprotein B (ApoB) levels in the plasma of treated animals [1] |
| Enzyme Assay |
PCSK9-LDLR binding inhibition assay (HTRF-based): Recombinant human PCSK9 and LDLR extracellular domain were mixed with serial dilutions of SBC-110736 in assay buffer. The mixture was incubated at 37°C for 1 hour, and the formation of PCSK9-LDLR complexes was detected using fluorescence resonance energy transfer. The inhibitory activity was calculated based on the fluorescence signal intensity relative to the vehicle control [1]
- Surface Plasmon Resonance (SPR) binding assay: SBC-110736 was immobilized on a sensor chip, and recombinant PCSK9 protein was injected at different concentrations. The binding affinity was determined by measuring the resonance signal changes, and the association and dissociation rates were calculated to assess the binding kinetics [1] |
| Cell Assay |
Hepatocyte LDL uptake assay: Human hepatoma cells were seeded in 96-well plates and incubated overnight. After serum starvation, the cells were pre-treated with SBC-110736 for 2 hours, followed by the addition of fluorescently labeled LDL. After 4 hours of incubation at 37°C, the cells were washed to remove unbound LDL, and the fluorescence intensity was measured to quantify the LDL uptake [1]
- LDLR degradation inhibition assay: Hepatoma cells were treated with SBC-110736 for 1 hour, then co-incubated with recombinant PCSK9 for 24 hours. The cells were lysed, and the protein extracts were subjected to immunoblotting to detect LDLR protein levels. Densitometric analysis was performed to compare LDLR expression relative to the internal control [1] - Cell viability assay: Hepatoma cells were seeded in 96-well plates and treated with a range of concentrations of SBC-110736 for 72 hours. A cell viability reagent was added, and the absorbance was measured to evaluate the cytotoxicity of the compound [1] |
| Animal Protocol |
Hypercholesterolemic mouse model: Male C57BL/6 mice were fed a high-cholesterol diet for 2 weeks to induce hypercholesterolemia. The mice were randomly divided into vehicle and treatment groups. SBC-110736 was dissolved in a mixture of aqueous solution with a solubilizing agent and administered intraperitoneally at doses of 10, 30, and 100 mg/kg once daily for 14 days. Blood samples were collected at baseline and the end of treatment to measure lipid parameters, and liver tissues were harvested for LDLR expression analysis [1]
- Pharmacokinetic study in rats: Male Sprague-Dawley rats were administered a single dose of SBC-110736 via intravenous and oral routes. Blood samples were collected at predetermined time points, and plasma concentrations of SBC-110736 were quantified using a validated analytical method. Pharmacokinetic parameters including half-life, clearance, and volume of distribution were calculated [1] |
| References | |
| Additional Infomation |
SBC-110736 is a small molecule PCSK9 inhibitor used to treat and/or prevent cardiovascular disease[1]. Its core mechanism of action is that SBC-110736 binds to PCSK9, blocking the interaction between PCSK9 and LDLR, thereby preventing LDLR degradation, increasing the uptake of LDL by the liver, and reducing plasma LDL-C levels[1]. This compound is suitable for the treatment of hypercholesterolemia (including familial hypercholesterolemia) and the prevention of atherosclerotic cardiovascular disease[1]. This compound is designed to overcome the limitations of existing lipid-lowering therapies, such as statin resistance or intolerance[1].
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| Molecular Formula |
C26H27N3O2
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|---|---|
| Molecular Weight |
413.5115
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| Exact Mass |
413.21
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| CAS # |
1629166-02-4
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| PubChem CID |
78425817
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
681.1±55.0 °C at 760 mmHg
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| Flash Point |
365.7±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.637
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| LogP |
3.09
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
602
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PILMFSWQYWYOJC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H27N3O2/c1-19-8-14-24(15-9-19)28-16-17-29(25(18-28)21-6-4-3-5-7-21)26(31)22-10-12-23(13-11-22)27-20(2)30/h3-15,25H,16-18H2,1-2H3,(H,27,30)
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| Chemical Name |
N-[4-(2-Phenyl-4-p-tolyl-piperazine-1-carbonyl)-phenyl]-acetamide
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| Synonyms |
SBC110736; SBC 110736; SBC-110736
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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 (~241.83 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.05 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 25.0 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: ≥ 2.5 mg/mL (6.05 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 25.0 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: ≥ 2.5 mg/mL (6.05 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 | 2.4183 mL | 12.0916 mL | 24.1832 mL | |
| 5 mM | 0.4837 mL | 2.4183 mL | 4.8366 mL | |
| 10 mM | 0.2418 mL | 1.2092 mL | 2.4183 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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