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| 1mg |
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| Targets |
GalNAc unconjugated/naked Fitusiran sodium targets antithrombin (AT, also known as SERPINC1) mRNA in the liver. As a synthetic siRNA, it is loaded into the RNA-induced silencing complex (RISC), where the antisense strand guides RISC to bind to the complementary sequence on antithrombin mRNA. This leads to the endonucleolytic cleavage and degradation of the mRNA, which in turn reduces antithrombin protein synthesis. Reduced AT levels promote increased thrombin generation, thereby enhancing coagulation. This mechanism is relevant for the treatment of bleeding disorders like hemophilia.
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| ln Vitro |
In vitro, GalNAc unconjugated/naked Fitusiran sodium is a small interfering RNA that specifically targets antithrombin (AT) messenger RNA to reduce AT production in the liver. The compound is the GalNAc-unconjugated version, which serves as a control for targeted delivery studies. The unconjugated siRNA has no targeting ligand and therefore has reduced uptake by hepatocytes compared to the GalNAc-conjugated version. No specific IC50 or EC50 values for AT knockdown are reported. The compound is used to study the mechanism of RNA interference and the effects of GalNAc conjugation on liver targeting.
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| ln Vivo |
No specific in vivo activity data for GalNAc unconjugated/naked Fitusiran sodium are reported in the search results. The GalNAc-conjugated version of Fitusiran (Fitusiran sodium) has been studied in clinical trials for hemophilia, where it reduces antithrombin levels and increases thrombin generation. The unconjugated version would not be expected to have significant in vivo activity due to its inability to efficiently enter hepatocytes without the GalNAc targeting ligand. The compound is for research use only as a control.
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| Enzyme Assay |
GalNAc unconjugated/naked Fitusiran sodium is an oligonucleotide; it does not bind directly to enzymes or receptors. Its binding to antithrombin mRNA is measured by standard hybridization assays. The thermal stability (Tm) of the siRNA:RNA duplex is assessed by UV melting curve analysis. The RNAi activity is confirmed in cell-free Dicer cleavage assays or in vitro RISC loading assays. The purity and identity are confirmed by HPLC and mass spectrometry. For analytical purposes, the siRNA is characterized by its sequence, molecular weight, and purity (typically >90%).
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| Cell Assay |
For cellular assays, human hepatoma cells (e.g., HepG2, Huh-7) are seeded in 6- or 12-well plates. GalNAc unconjugated/naked Fitusiran sodium is added to the culture medium at concentrations of 1-1000 nM. The siRNA is typically delivered using a transfection reagent (e.g., Lipofectamine RNAiMAX) because the unconjugated version has poor cell uptake. After 24-72 hours of incubation, cells are harvested. Antithrombin (AT/SERPINC1) mRNA levels are quantified by qRT-PCR. Antithrombin protein levels in the culture medium are measured by ELISA. Cytotoxicity is assessed by MTT or LDH assays. The GalNAc-conjugated version is used in parallel to compare delivery efficiency.
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| Animal Protocol |
No animal experiments for GalNAc unconjugated/naked Fitusiran sodium are described in the search results. For in vivo evaluation of the unconjugated siRNA, 6-8-week-old female C57BL/6 mice would be used. The compound would be administered intravenously (IV) at doses of 1-30 mg/kg. The GalNAc-conjugated version would be used as a positive control. Blood would be collected at multiple time points (0, 24, 48, 72 h, and up to 21 days) to measure antithrombin protein levels by ELISA. Livers would be harvested for quantification of antithrombin mRNA by qPCR. The unconjugated siRNA is expected to have significantly less activity in the liver compared to the GalNAc-conjugated version due to lack of targeted delivery. No such data are provided.
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| ADME/Pharmacokinetics |
GalNAc unconjugated/naked Fitusiran sodium is an siRNA with a molecular weight of approximately 14,000-17,000 Da. It is a white to off-white solid powder. For storage, the powder should be kept at -20degC or -80degC, sealed, and protected from moisture. 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. For in vivo use, it can be formulated in saline or PBS. The compound is typically used as a control; no detailed PK parameters are reported for the unconjugated version. The GalNAc-conjugated version is expected to have a longer circulation half-life and greater liver accumulation.
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| Toxicity/Toxicokinetics |
No specific toxicity data for GalNAc unconjugated/naked Fitusiran sodium are reported. SiRNAs in general can cause off-target effects, immune stimulation (via TLR3, TLR7, TLR8, RIG-I), and hepatotoxicity at high doses. The GalNAc-conjugated version has been evaluated in clinical trials and has shown a generally acceptable safety profile. As a research-grade compound, 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. No LD50 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
GalNAc unconjugated/naked Fitusiran sodium is the GalNAc-free form of Fitusiran, an investigational siRNA therapeutic for hemophilia A and B. Fitusiran targets antithrombin (AT) mRNA in the liver, reducing AT production and increasing thrombin generation. The GalNAc (N-acetylgalactosamine) conjugation targets the asialoglycoprotein receptor (ASGPR) on hepatocytes, enabling efficient liver delivery. The unconjugated version lacks the GalNAc ligand and serves as a research control to evaluate the effect of GalNAc conjugation on liver targeting. Fitusiran (the GalNAc-conjugated version) is in clinical development for hemophilia. The compound is for research use only and has not received regulatory approval for any indication.
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| Molecular Weight |
14459.60
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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, 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.0692 mL | 0.3458 mL | 0.6916 mL | |
| 5 mM | 0.0138 mL | 0.0692 mL | 0.1383 mL | |
| 10 mM | 0.0069 mL | 0.0346 mL | 0.0692 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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