| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
PCSK9 mRNA. SPC5001 is a synthetic antisense oligonucleotide that binds to a complementary sequence on the human PCSK9 mRNA. This binding triggers ribonuclease H (RNase H)-mediated degradation of the mRNA transcript, thereby preventing the translation of the PCSK9 protein and reducing circulating PCSK9 levels.
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| ln Vitro |
SPC5001 (0.16–40 µM; 72 h) downregulates the targets of PCSK9 mRNA, however in 2D human renal proximal tubule epithelial cells (HRPTEC) cultures, cytotoxicity is not seen at any concentration[1]. In chip-cultured HRPTEC, SPC5001(5 µM; 48 h or 20 d) downregulates PCSK9 mRNA by 74.1% and 93.7% for 48 h and 20 days, respectively[1]. In chip-cultured HRPTEC, SPC5001 (5 µM; 20 d) causes cytotoxicity and raises perfusate levels of biomarkers KIM-1, NGAL, clusterin, osteopontin, and VEGF[1].
In vitro studies in primary human hepatocytes showed that SPC5001 treatment leads to a potent and dose-dependent reduction of PCSK9 mRNA and protein levels. The antisense mechanism is LNA-enhanced, providing high binding affinity and stability, which results in sustained target suppression. This reduction in PCSK9 leads to an upregulation of the LDL receptor on hepatocyte surfaces. |
| ln Vivo |
In vivo, a first-in-human trial demonstrated that SPC5001 could dose-dependently inhibit PCSK9 and reduce LDL-C concentrations. At the highest dose tested (5 mg/kg), SPC5001 decreased target protein PCSK9 by 49% compared to placebo and reduced LDL-C by up to 0.72 mmol/L. It also decreased ApoB and increased ApoA1, establishing human proof-of-pharmacology, though clinical development was terminated.
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| Enzyme Assay |
Non-cell-based target engagement assays are not directly applicable for ASOs. However, hybridization-based assays (e.g., Northern blot or branched DNA assays) are used to confirm the binding of SPC5001 to its target PCSK9 mRNA in vitro. These methods quantify the remaining full-length PCSK9 mRNA after treatment, validating the mechanism of action.
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| Cell Assay |
Primary human hepatocytes are cultured in 96-well plates. Cells are treated with SPC5001 at concentrations from 0.1 nM to 1 uM using lipid-based transfection or gymnotic delivery (without a carrier). After 24-72 hours, RNA is extracted. PCSK9 mRNA knockdown is quantified by RT-qPCR. Cell culture supernatants are collected to measure secreted PCSK9 protein levels by ELISA.
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| Animal Protocol |
First-in-human trial: Healthy volunteers received three weekly subcutaneous administrations of SPC5001 at doses of 0.5, 1.5, or 5 mg/kg. The primary endpoints were safety, tolerability, and pharmacokinetics. Pharmacodynamic efficacy was measured by serial blood collections to quantify serum PCSK9 and LDL-C levels over a period of 4-6 weeks. Renal function was monitored via serum creatinine and urine analysis.
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| ADME/Pharmacokinetics |
In the human trial, SPC5001 plasma exposure (AUC(0,24h)) increased more than dose-proportionally. The compound exhibited a long plasma half-life consistent with LNA-modified oligonucleotides, allowing for once-weekly subcutaneous administration. Pharmacodynamic effects on PCSK9 and LDL-C levels persisted for weeks after the last dose, indicating a prolonged duration of action.
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| Toxicity/Toxicokinetics |
The clinical development of SPC5001 was terminated due to toxicity. Treatment at the 5 mg/kg dose was associated with injection site reactions (in 44% of subjects) and transient renal tubular toxicity, including elevated serum creatinine and one case of biopsy-proven acute tubular necrosis. At lower doses (0.5 and 1.5 mg/kg), the safety profile was more favorable.
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| References | |
| Additional Infomation |
SPC5001 was an investigational drug candidate whose development was halted. It is now available as a research compound only to study antisense mechanisms, PCSK9 biology, and oligonucleotide toxicity. It is not approved for human therapeutic use. The compound has a molecular weight of 4689.85 and is supplied as a sodium salt, which should be stored at -20degC to prevent degradation.
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| Molecular Weight |
4689.85
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| Appearance |
White to off-white 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, 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 :≥ 100 mg/mL (~21.32 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 | 0.2132 mL | 1.0661 mL | 2.1323 mL | |
| 5 mM | 0.0426 mL | 0.2132 mL | 0.4265 mL | |
| 10 mM | 0.0213 mL | 0.1066 mL | 0.2132 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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