| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Transthyretin (TTR) mRNA. The GalNAc moiety enables highly efficient and specific delivery to hepatocytes via the asialoglycoprotein receptor (ASGPR). Once internalized, vutrisiran silences TTR mRNA by RNA interference, reducing the production of both wild-type and mutant TTR protein.
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| ln Vitro |
An investigational RNAi treatment of the second generation, vutrisiran (formerly known as ALN-TTRSC02), is being developed to treat ATTR amyloidosis. Targeting a region within the TTR mRNA that is conserved in both WT and all known TTR variants, vutrisiran comprises a siRNA. To enable infrequent subcutaneous (SC) dosing, the Vutrisiran siRNA, on the other hand, conjugates to a triantennary GalNAc ligand via enhanced stabilization chemistry (ESC)[1].
In vitro, vutrisiran demonstrates potent and specific silencing of TTR mRNA in primary human hepatocytes with an IC50 in the picomolar range. The GalNAc conjugation enhances hepatocyte uptake by up to 10-20 fold compared to unconjugated siRNA, leading to TTR protein knockdown exceeding 90% in cell culture. |
| ln Vivo |
Single SC doses of Vutrisiran 0.3 and 1 mg/kg in non-human primates produced mean maximal TTR reductions (nadirs) of 55% and 96%, respectively, with the 1 mg/kg dose resulting in serum TTR reductions that lasted longer than four months. Monthly dosages of 1 and 3 mg/kg in the same research kept the reduction in TTR levels at 96% compared to baseline[1].
In vivo, vutrisiran suppresses serum TTR levels by over 90% in mouse and non-human primate models at low subcutaneous doses (1-3 mg/kg). In humans, the Phase 3 HELIOS-A trial showed that vutrisiran achieved rapid and sustained TTR lowering, with mean serum TTR reduction exceeding 80% throughout the dosing interval (once every 3 months). |
| Enzyme Assay |
No specific cell-free binding assays are applicable for vutrisiran as it is an RNAi agent. Target engagement is assessed via measurement of TTR mRNA knockdown. For determination of ASGPR binding affinity, competitive binding assays using radiolabeled asialoglycoproteins and GalNAc-conjugated compounds can be performed on isolated hepatocyte membranes.
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| Cell Assay |
Primary human hepatocytes or Huh-7 cells are seeded and treated with vutrisiran (concentration range 0.01 pM to 10 nM) for 24-72 hours. TTR mRNA levels are quantified by RT-qPCR normalized to housekeeping genes (e.g., GAPDH). TTR protein in cell culture supernatants is measured by ELISA. Cellular uptake efficiency can be monitored using fluorescently labeled vutrisiran by flow cytometry or confocal microscopy.
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| Animal Protocol |
Animal studies (mice, rats, or cynomolgus monkeys) are used to evaluate TTR knockdown. Vutrisiran is administered subcutaneously (0.3-10 mg/kg). Blood samples are collected at various time points up to 30 days post-dose. Serum TTR levels are quantified by ELISA. Liver samples are harvested at necropsy for measurement of TTR mRNA via RT-qPCR. HEK293 or CHO-K1 cells are transiently transfected with ASGPR1/2 to assess vutrisiran uptake and silencing activity. Vutrisiran is rapidly absorbed (peak plasma concentration 3-5 hours post-dose), median terminal elimination half-life (t1/2) 5.23 hours (range 2.24-6.36 hours). Apparent plasma clearance 21.4 L/h after 25 mg SC dose. Volume of distribution 10.1 L. Mean fraction excreted unchanged in urine 15.4-25.4%.
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| ADME/Pharmacokinetics |
In animal toxicology studies (rats and monkeys), vutrisiran demonstrated a favorable safety profile at clinically relevant doses. The most common adverse events in clinical trials are injection site reactions (pain, erythema, swelling). No drug-related hepatotoxicity or renal toxicity has been observed in clinical studies to date.
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| Toxicity/Toxicokinetics |
Other information: Vutrisiran (Amvuttra) is FDA-approved for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) and ATTR cardiomyopathy (ATTR-CM). It is administered subcutaneously at 25 mg once every 3 months, offering a significant dosing convenience over patisiran (IV once every 3 weeks). Approved in 2022.
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| References |
| CAS # |
1867157-35-4
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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: ≥ 20 mg/mL
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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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