| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Volanesorsen targets apolipoprotein C-III (APOC3) mRNA through complementary base pairing. The antisense oligonucleotide binds to APOC3 mRNA, leading to RNase H-mediated degradation of the transcript, thereby preventing APOC3 protein synthesis. Reduced APOC3 levels increase lipoprotein lipase activity and hepatic clearance of triglyceride-rich lipoproteins.
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| ln Vitro |
In vitro, Volanesorsen reduces APOC3 mRNA and protein levels in primary human hepatocytes. It decreases triglyceride secretion and increases lipoprotein lipase-mediated lipolysis. Cellular studies demonstrate concentration-dependent knockdown of APOC3 with minimal off-target effects. EC50 values are in the low nanomolar range.
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| ln Vivo |
In vivo, Volanesorsen (subcutaneous administration) reduces hepatic APOC3 mRNA and protein levels and decreases serum APOC3, VLDL-C, and triglycerides in animal models. In transgenic mice expressing human APOC3, Volanesorsen produces dose- and time-dependent reductions in triglycerides. Clinical trials demonstrate triglyceride reductions of up to 70-80% in FCS patients.
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| Enzyme Assay |
Not applicable; as an antisense oligonucleotide, Volanesorsen is not evaluated in traditional enzyme/receptor binding assays. Target engagement is assessed by measuring APOC3 mRNA levels in cells or tissues using qRT-PCR or Northern blot.
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| Cell Assay |
For cell-based assays, primary human hepatocytes or HepG2 cells are transfected with Volanesorsen (0.1-10 uM) using lipofection. After 24-72 hours, APOC3 mRNA is quantified by qRT-PCR, and APOC3 protein levels in culture supernatant are measured by ELISA. Cytotoxicity is assessed by MTT or LDH release assays.
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| Animal Protocol |
For in vivo evaluation, human APOC3 transgenic mice receive subcutaneous injections of Volanesorsen (10-50 mg/kg) twice weekly for 2-4 weeks. Blood samples are collected for lipid panel analysis. Liver tissue is harvested for APOC3 mRNA quantification by qRT-PCR and for histopathological examination. In clinical studies, FCS patients receive subcutaneous Volanesorsen (300 mg once weekly) and are monitored for triglyceride levels, adverse events, and immune responses.
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| ADME/Pharmacokinetics |
Volanesorsen is administered by subcutaneous injection. In healthy volunteers, it exhibits dose-dependent absorption with Tmax of 2-4 hours. The plasma half-life is approximately 1-2 weeks due to high protein binding and resistance to nuclease degradation. It is metabolized by nucleases and excreted in urine, primarily as shorter oligonucleotide fragments. No significant CYP450 interactions have been reported.
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| Toxicity/Toxicokinetics |
Common adverse events include injection site reactions (erythema, pain), thrombocytopenia (occurring in approximately one-third of patients), and hepatotoxicity. Anemia was the most common cause for treatment discontinuation. Ocular injuries and immune complex deposition have also been reported.
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| References | |
| Additional Infomation |
See also: Volanesorsen (note moved to).
Drug Indications Waylivra is indicated for adult patients with genetically confirmed familial chylomicronemia syndrome (FCS) as adjunctive therapy to diet, who are at high risk of pancreatitis and have had an inadequate response to diet and triglyceride-lowering therapies. Waylivra received conditional marketing authorization from the European Medicines Agency (EMA) in 2019 for familial chylomicronemia syndrome. It has not been approved by the FDA due to safety concerns. Volanesorsen is the first approved antisense oligonucleotide for FCS. Ongoing research explores its use in other hypertriglyceridemic conditions. |
| CAS # |
915430-78-3
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|---|---|
| PubChem CID |
121494123
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
44
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| Hydrogen Bond Acceptor Count |
162
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| Rotatable Bond Count |
156
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| Heavy Atom Count |
456
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| Complexity |
20400
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| Defined Atom Stereocenter Count |
70
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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) |
H2O : ~50 mg/mL (~6.98 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.) |
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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