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Purity: ≥98%
SBC-115076 (SBC115076) is a potent extracellular proprotein convertase subtilisin kexin type 9 (PCSK9) antagonist, with the potential for the treatment and/or prevention of cardiovascular diseases. SBC-115076 showed a dose-dependent increase of the DHLDL uptake, which was lower than that SBC-110034 did. Moreover, SBC-115076 could increase several folds of the intracellular LDLR level at 1.6 μM. SBC-115076 was observed to lower cholesterol levels in mice that were fed high fat diet. Results showed data obtained with SBC-115076 indicating a mean of 32% reduction in total cholesterol levels after two weeks relative to high fat diet animal levels and a mean 50% reduction toward return to regular diet cholesterol levels
| Targets |
SBC-115076 targets proprotein convertase subtilisin/kexin type 9 (PCSK9) [1]
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| ln Vitro |
In vitro activity: In HepG2 cells, SBC-115076 increases the uptake of Fluorescent Dil-LDL. It was found that SBC-115076 could dose-dependently increase the DHLDL uptake, which was lower than that SBC-110034 did. Moreover, SBC-115076 could increase several folds of the intracellular LDLR level at 1.6 μM
Cell Assay: It was found that SBC-115076 could dose-dependently increase the DHLDL uptake, which was lower than that SBC-110034 did. Moreover, SBC-115076 could increase several folds of the intracellular LDLR level at 1.6 μM |
| ln Vivo |
In high-fat-fed rats, SBC-115076 (4 mg/kg; subcutaneous injection; once daily for 3 weeks) increases insulin sensitivity and decreases adiposity and dyslipidemia [1].
In obese-insulin resistant (OIR) female Wistar rats induced by a high-fat diet (HFD), oral administration of SBC-115076 (10 mg/kg/day for 8 weeks) significantly reduced serum total cholesterol (TC) by 32% and low-density lipoprotein cholesterol (LDL-C) by 40% compared to OIR control rats, without affecting high-density lipoprotein cholesterol (HDL-C) or triglyceride (TG) levels [1] SBC-115076 protected mitochondria in oxidative muscle fibers (soleus muscle): increased the activities of mitochondrial respiratory chain complexes I, III, and IV by 28%, 35%, and 30% respectively; reduced mitochondrial reactive oxygen species (ROS) production by 45% and lipid peroxidation (malondialdehyde, MDA) levels by 42%; and enhanced superoxide dismutase (SOD) activity by 38% [1] Histopathological analysis showed SBC-115076 maintained mitochondrial morphology in oxidative muscle fibers, reducing mitochondrial swelling and cristae disruption compared to OIR control. It also decreased muscle oxidative stress markers (8-OHdG) by 36% [1] |
| Animal Protocol |
Animal/Disease Models: Female Wistar rats (high-fat diet (HFD)- fed)[1]
Doses: 4 mg/kg Route of Administration: Sc; daily for 3 weeks Experimental Results: Superior to atorvastatin in instigating weight loss, cholesterol reduction, and attenuation of Mitochondrial oxidative stress in oxidative muscle fibers of obese female rats. OIR rat model establishment: Female Wistar rats (6 weeks old) were fed a high-fat diet (HFD, 60% fat calories) for 16 weeks to induce obesity and insulin resistance. Rats were then randomly divided into three groups (n=8/group): OIR control group (vehicle), atorvastatin group (80 mg/kg/day), and SBC-115076 group (10 mg/kg/day) [1] Drug administration: SBC-115076 was suspended in 0.5% carboxymethylcellulose sodium solution, administered via oral gavage once daily for 8 weeks. The control group received the same volume of vehicle, and the atorvastatin group was treated with atorvastatin via the same route and frequency [1] Sample collection: At the end of treatment, rats were anesthetized, blood samples were collected to measure serum lipid profiles and biochemical markers. Soleus muscle (oxidative muscle) was harvested for mitochondrial function analysis, oxidative stress detection, and histopathological examination [1] |
| Toxicity/Toxicokinetics |
During the 8-week treatment period, SBC-115076 (10 mg/kg/day, orally) did not cause significant changes in body weight (change <5%) compared to the OIR control group rats [1]. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), and blood urea nitrogen (BUN) levels were all within the normal range, indicating that no obvious hepatotoxicity or nephrotoxicity was observed [1]. No increase in serum creatine kinase (CK) was observed, suggesting that SBC-115076 did not cause skeletal muscle damage [1].
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| References |
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| Additional Infomation |
SBC-115076 is a small molecule PCSK9 inhibitor. PCSK9 is a protein that promotes the degradation of LDL receptors in the liver[2]. Its core mechanism of action is to inhibit PCSK9, thereby increasing the number of LDL receptors on the hepatocyte membrane, enhancing the clearance of circulating LDL-C, and reducing serum LDL-C levels[2]. In an oxygen-induced inflammatory response (OIR) rat model, SBC-115076 exerts a protective effect on oxidized myofibril mitochondria by reducing oxidative stress and improving mitochondrial respiratory chain function, and this effect is independent of its lipid-lowering effect[1]. PCSK9 inhibitors are used clinically to treat hypercholesterolemia, especially for patients who are intolerant to statins or whose LDL-C reduction is insufficient[2].
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| Molecular Formula |
C31H33N3O5
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| Molecular Weight |
527.61
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| Exact Mass |
527.242
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| CAS # |
489415-96-5
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| Related CAS # |
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| PubChem CID |
5734410
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.0 g/cm3
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| Boiling Point |
754.2±0.0 °C at 760 mmHg
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| Flash Point |
409.9±0.0 °C
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| Vapour Pressure |
0.0±0.0 mmHg at 25°C
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| Index of Refraction |
1.624
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| LogP |
3.47
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
39
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| Complexity |
860
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=CC(=C1)/C(=C\2/C(N(C(=O)C2=O)CCCN3CCOCC3)C4=CC=NC=C4)/O)OCC5=CC=CC=C5
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| InChi Key |
VVYIXKBHQQSREP-ORIPQNMZSA-N
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| InChi Code |
InChI=1S/C31H33N3O5/c1-22-20-25(8-9-26(22)39-21-23-6-3-2-4-7-23)29(35)27-28(24-10-12-32-13-11-24)34(31(37)30(27)36)15-5-14-33-16-18-38-19-17-33/h2-4,6-13,20,28,35H,5,14-19,21H2,1H3/b29-27+
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| Chemical Name |
(4E)-4-[hydroxy-(3-methyl-4-phenylmethoxyphenyl)methylidene]-1-(3-morpholin-4-ylpropyl)-5-pyridin-4-ylpyrrolidine-2,3-dione
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.74 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 (4.74 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 (4.74 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 | 1.8953 mL | 9.4767 mL | 18.9534 mL | |
| 5 mM | 0.3791 mL | 1.8953 mL | 3.7907 mL | |
| 10 mM | 0.1895 mL | 0.9477 mL | 1.8953 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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