| Targets |
SPC5001 sodium targets PCSK9 mRNA. PCSK9 is a protein that binds to the LDL receptor (LDLR) and targets it for degradation, leading to reduced LDL uptake from the circulation. As an antisense oligonucleotide, SPC5001 binds to its complementary sequence on PCSK9 mRNA via Watson-Crick base pairing, leading to RNase H-mediated degradation of the mRNA, which in turn reduces PCSK9 protein synthesis. This results in increased LDLR levels on the cell surface and enhanced clearance of LDL-cholesterol from the blood.
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| ln Vitro |
SPC5001 sodium is an antisense oligonucleotide (ASO) that is complementary to human PCSK9 mRNA. In vitro, SPC5001 binds to PCSK9 mRNA and induces its degradation via an RNase H-dependent mechanism, leading to a reduction in PCSK9 protein levels. By reducing PCSK9 expression, the compound upregulates the LDL receptor (LDLR), enhancing LDL-cholesterol uptake. No specific IC50 or EC50 values are reported in the search results. The LNA modification increases the stability and binding affinity of the ASO.
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| ln Vivo |
No specific in vivo activity data for SPC5001 sodium are reported in the search results. As a PCSK9-targeting ASO, it has potential for use in mouse models of hypercholesterolemia, such as human PCSK9 transgenic mice or ApoE-/- mice fed a high-fat diet. When administered systemically, it is expected to reduce PCSK9 mRNA and protein levels in the liver, leading to a reduction in plasma LDL-cholesterol levels. SPC5001 is a research-grade ASO and has not received regulatory approval.
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| Enzyme Assay |
SPC5001 sodium is an oligonucleotide; it does not bind to enzymes or receptors. Its binding to PCSK9 mRNA is measured by standard hybridization assays. The affinity is typically determined by the melting temperature (Tm) of the ASO:RNA duplex. SPC5001 is incubated with a complementary RNA oligonucleotide, and the temperature is increased while measuring UV absorbance at 260 nm. The Tm is the temperature at which half of the duplex is denatured. LNA modification increases the Tm, which correlates with higher binding affinity. No specific Tm value is reported.
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| Cell Assay |
For in vitro assays, human hepatoma cells (e.g., HepG2, Huh-7, or primary human hepatocytes) are seeded in 6- or 12-well plates. SPC5001 sodium is added to the culture medium at concentrations of 1-1000 nM using a transfection reagent (e.g., lipofectamine) or by free uptake (gymnosis). After 24-72 hours of incubation, cells are harvested. PCSK9 mRNA levels are quantified by qRT-PCR using TaqMan or SYBR Green assays. PCSK9 protein levels in the culture medium (secreted) are measured by ELISA. LDLR protein levels in cell lysates are measured by Western blot. Functionally, the uptake of fluorescently labeled LDL (DiI-LDL) is measured by flow cytometry to assess LDLR activity.
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| Animal Protocol |
No animal experiments for SPC5001 sodium are described in the search results. For in vivo evaluation of PCSK9 knockdown, 6-8-week-old female human PCSK9 transgenic mice or C57BL/6 mice (with AAV8-mediated delivery of human PCSK9) are used. SPC5001 sodium is administered subcutaneously (SC) or intravenously (IV) at doses of 10-100 mg/kg once weekly for 2-4 weeks. Blood is collected, and plasma levels of PCSK9 protein are measured by ELISA. Plasma lipid profiles (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) are measured by enzymatic assays. At the study endpoint, livers are harvested for quantification of PCSK9 mRNA by qPCR and PCSK9 and LDLR protein levels by Western blot.
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| ADME/Pharmacokinetics |
SPC5001 sodium (MW = 5011.70) is a white to off-white solid powder. For storage, the powder should be kept at -20degC for up to 3 years, sealed, and protected from moisture (preferably stored under nitrogen). For in vitro use, stock solutions in nuclease-free water or PBS (1-10 mg/mL) can be prepared and stored at -20degC or -80degC. Avoid repeated freeze-thaw cycles. The ASO is stable in solution at -80degC for up to 6 months or at -20degC for up to 1 month. For in vivo use, it can be formulated in saline or PBS. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for SPC5001 sodium are reported. As a research-grade ASO, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling oligonucleotides should be followed, including the use of gloves, lab coat, and safety goggles. ASOs can be hepatotoxic at high doses, and the LNA modification can increase the risk of hepatotoxicity. No LD50 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
SPC5001 sodium is an LNA-modified antisense oligonucleotide targeting PCSK9. PCSK9 is a well-validated target for lowering LDL-cholesterol. Monoclonal antibodies against PCSK9 (e.g., evolocumab, alirocumab) are approved for the treatment of hypercholesterolemia, and an siRNA therapeutic (inclisiran) is also approved. SPC5001 is a research-grade ASO that predated the clinical development of inclisiran. The compound is for research use only and has not received regulatory approval.
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| Appearance |
Solid powder
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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 (e.g. under nitrogen), 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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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