| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
Alpha-1 antitrypsin (AAT) mRNA.
|
|---|---|
| ln Vitro |
Fazirsiran consists of a cholesterol-conjugated RNAi trigger (chol-RNAi) that is delivered to hepatocytes. It is co-formulated with a melittin-derived peptide conjugated to N-acetylgalactosamine (NAG) which acts as an excipient to promote endosomal escape, enabling the RNAi trigger to reach the RNAi machinery and degrade AAT mRNA.
|
| ln Vivo |
In five-week-old male PiZ mice, nazirsiran (ARO-AAT; sc; 4 mg/kg; on 1, 15, 29, 43 days during 57 days) significantly decreases Z-AAT mRNA and protein[1].
In animal models (e.g., transgenic mice expressing mutant human AAT), administration of Fazirsiran leads to a significant, dose-dependent reduction in serum levels of total AAT and polymerized mutant AAT, which is the pathological species causing liver disease in Alpha-1 antitrypsin deficiency (AATD). |
| Enzyme Assay |
This is not a standard enzyme/inhibitor assay. Activity is measured by quantifying the mRNA knockdown efficiency. For example, cultured primary human hepatocytes are treated with Fazirsiran (1-100 nM), and the remaining AAT mRNA is quantified by RT-qPCR to calculate the EC50 for mRNA degradation.
|
| Cell Assay |
Cells (e.g., human hepatocytes or cell lines expressing mutant AAT) are treated with various concentrations of Fazirsiran. After 48-72 hours, intracellular and secreted AAT protein levels are measured by ELISA or Western blot. Total RNA is extracted from cell pellets and analyzed by RT-qPCR to assess AAT mRNA levels.
|
| Animal Protocol |
Transgenic mice expressing human PiZ AAT are dosed subcutaneously with Fazirsiran (e.g., 1, 3, or 10 mg/kg). Serum is collected at regular intervals to measure AAT protein levels by ELISA. Liver tissue is harvested at study termination for analysis of AAT protein and mRNA by Western blot and RT-qPCR.
|
| ADME/Pharmacokinetics |
Fazirsiran is administered subcutaneously. As an RNAi therapeutic, it has a prolonged duration of action, allowing for infrequent dosing (e.g., monthly or quarterly). Its PK profile is characterized by rapid absorption into systemic circulation and distribution to the liver, with a half-life supporting sustained target engagement.
|
| Toxicity/Toxicokinetics |
In preclinical toxicology studies, Fazirsiran is generally well-tolerated. The primary potential toxicities are related to off-target RNAi effects or immune stimulation. No significant hepatotoxicity or nephrotoxicity was observed in animal models at pharmacologically active doses.
|
| References | |
| Additional Infomation |
Fazirsiran (ARO-AAT) has been investigated in Phase 2 clinical trials for the treatment of Alpha-1 Antitrypsin Deficiency (AATD) with associated liver disease. It is one of the leading RNAi-based therapeutics targeting a genetic liver disease, demonstrating proof-of-mechanism by significantly reducing the pathogenic Z-AAT protein.
|
| CAS # |
2175009-08-0
|
|---|---|
| Appearance |
White to off-white solid powder
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
