| Size | Price | Stock | Qty |
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| 1mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Transthyretin (TTR) mRNA. Patisiran binds to the 3‘ untranslated region of TTR mRNA, leading to its degradation via RNA interference (RNAi) mechanism, thereby reducing the production of both wild-type and mutant TTR proteins in the liver.
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| ln Vitro |
Patisiran sodium selectively binds to genetically conserved regions in the 3' untranslated region of both mutant and wild-type transthyretin (TTR) messenger RNA, causing TTR breakdown (by RNA interference) and ultimately reducing serum TTR protein levels and tissue TTR. protein accumulation[2].
In vitro, patisiran (formulated in LNPs) demonstrates concentration-dependent silencing of TTR mRNA in human hepatoma cell lines (e.g., HepG2 and HuH-7) with an IC50 in the picomolar to low nanomolar range. It reduces secreted TTR protein levels by over 90% at optimal concentrations. |
| ln Vivo |
In preclinical mouse models of ATTR, intravenous administration of patisiran results in robust, dose-dependent reduction of serum TTR levels by up to 90-95%, which is sustained for several weeks. Efficacy in humans was confirmed in the Phase 3 APOLLO study in hATTR patients with polyneuropathy.
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| Enzyme Assay |
Measurement of TTR knockdown via branched DNA (bDNA) or qRT-PCR. Human hepatocytes or primary mouse hepatocytes are seeded and treated with patisiran LNPs for 24-48 hours. Total RNA is extracted and TTR mRNA levels are quantified by RT-qPCR normalized to GAPDH. Target knockdown is expressed as percentage of TTR mRNA remaining relative to untreated control.
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| Cell Assay |
Human hepatoma cells (HepG2 or HuH-7) are seeded in 96-well plates and treated with patisiran LNPs at various concentrations (0.01 pM to 1 nM) for 24-48 hours. Cell culture supernatants are collected and TTR protein levels are measured by ELISA. Cellular TTR mRNA is extracted and analyzed by RT-qPCR. Cell viability is assessed by MTT or CellTiter-Glo to ensure target knockdown is not due to cytotoxicity.
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| Animal Protocol |
Transgenic mice expressing human TTR are administered patisiran via intravenous tail vein injection (0.1-3 mg/kg). Blood samples are collected at various time points up to day 21 post-dose. Serum TTR levels are quantified by ELISA or mass spectrometry to assess pharmacodynamic response. For efficacy, treated mice are challenged with TTR aggregates to assess protection.
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| ADME/Pharmacokinetics |
PK: mean steady-state volume of distribution (Vss) 0.26 +/- 0.20 L/kg; total body clearance (CLss) 3.0 +/- 2.5 mL/h/kg; terminal elimination half-life 3.2 +/- 1.8 days; plasma protein binding less than 2.1%; dose-proportional exposure across 0.01-0.3 mg/kg; primarily cleared via metabolism.
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| Toxicity/Toxicokinetics |
Toxicology studies in animals (rats and monkeys) demonstrated that patisiran is generally well-tolerated at therapeutic doses, with the primary adverse events being infusion-related reactions (e.g., flushing, back pain, nausea) and mild elevations in liver transaminases. In humans, the most common side effects include peripheral edema and infusion site reactions.
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| References |
[1]. Adams D, et, al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21.
[2]. Hoy SM. Patisiran: First Global Approval. Drugs. 2018 Oct;78(15):1625-1631. [3]. Kristen AV, et, al. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neurodegener Dis Manag. 2019 Feb;9(1):5-23. |
| Additional Infomation |
Other information: Patisiran (Onpattro) is approved for the treatment of polyneuropathy in adult patients with hereditary transthyretin-mediated amyloidosis (hATTR). The recommended dose is 0.3 mg/kg administered via intravenous infusion once every 3 weeks. Approved by FDA (2018) and EMA.
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| Molecular Weight |
13427.10 (AS: 6661.3; SS: 6765.8)
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| CAS # |
1386913-72-9
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| Appearance |
Off-white to light yellow 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) |
H2O: 33.33 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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