| Size | Price | Stock | Qty |
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| 1mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
TTR/transthyretin; asialoglycoprotein receptor
Eplontersen targets transthyretin (TTR) mRNA. As an antisense oligonucleotide, it binds to both wild-type and variant TTR mRNA, recruiting RNase H which degrades the mRNA transcript. This mechanism reduces the production of TTR protein in the liver. By decreasing the levels of circulating TTR protein, eplontersen reduces the formation and deposition of amyloid fibrils in tissues such as nerves and the heart. The GalNAc conjugation enhances liver-specific uptake, allowing for potent and targeted gene silencing with infrequent dosing. |
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| ln Vitro |
N-acetylgalactosamine moiety is mediated by Eplontersen to direct oligonucleotides to cells that express asialoglycoprotein receptors [3].
In vitro studies demonstrate that eplontersen effectively binds to its target TTR mRNA. The GalNAc moiety mediates the targeting of eplontersen to cells that express the asialoglycoprotein receptor, such as hepatocytes. In cell-based assays, the compound shows potent and specific inhibition of TTR protein expression. It has been shown to reduce TTR mRNA and protein levels in a dose-dependent manner in cells expressing human TTR. |
| ln Vivo |
Eplontersen (682884) (0.6, 2, 6 mg/kg; subcutaneous injection; once weekly for 3 weeks) inhibits TTR protein expression in a dose-dependent manner in vivo without affecting transgenic C57BL/ expressing human transthyretin. 6 Normal growth of mice. TTR)[3].
In vivo, eplontersen has demonstrated significant efficacy in reducing serum TTR levels and improving clinical outcomes in patients with ATTRv-PN. In transgenic C57BL/6 mice expressing human TTR, subcutaneous administration of eplontersen at 6 mg/kg once weekly for 3 weeks reduced TTR mRNA levels to 15% and plasma TTR protein levels to 21% on day 17. In a Phase III trial (NEURO-TTRansform), subcutaneous eplontersen reduced serum TTR levels, inhibited neuropathy progression, and improved health-related quality of life in patients with ATTRv-PN. In preregistration open-label studies, it decreased TTR levels and led to improvements in neuropathy symptoms and quality of life. |
| Enzyme Assay |
In vitro non-cell-based assays for eplontersen typically involve measuring its binding affinity to target TTR mRNA or assessing its ability to induce RNase H-mediated cleavage of the mRNA. These assays often use cell-free systems with purified components to evaluate the oligonucleotide's hybridization and degradation activity. Surface plasmon resonance (SPR) or other biophysical techniques can be used to determine binding kinetics. The compound's ability to recruit RNase H and cleave the target RNA can be assessed using gel-based or fluorescence-based assays.
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| Cell Assay |
In vitro cell-based assays for eplontersen are conducted in cell lines that express TTR, such as HepG2 cells. Cells are treated with varying concentrations of eplontersen for a specified duration (e.g., 24-72 hours). TTR mRNA levels are quantified using quantitative PCR (qPCR), and TTR protein levels are measured using ELISA or Western blotting. The compound's potency (IC50) and efficacy are determined from the dose-response curves. Cytotoxicity is assessed using standard cell viability assays (e.g., MTT) to ensure specificity.
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| Animal Protocol |
Animal/Disease Models: Transgenic C57BL/6 mice (8 weeks old) expressing human transthyretin (TTR) [3]
Doses: 0.6, 2, 6mg/kg Route of Administration: subcutaneous injection; once a week for 3 weeks ; Tail bleeding was performed at different time points; the mice were sacrificed 72 hrs (hrs (hours)) after the final administration. Experimental Results: On day 17 after injection, the TTR mRNA level at 6 mg/kg diminished to 15%, and the plasma TTR protein level diminished to 21%. There was no significant effect on plasma ALT and AST levels, and no inhibitory effect on body weight, organ weight, spleen weight, and kidney weight. In vivo animal studies for eplontersen are conducted in transgenic C57BL/6 mice (8 weeks old) expressing human TTR. The compound is administered subcutaneously at doses of 0.6, 2, and 6 mg/kg once a week for 3 weeks. Tail bleeding is performed at different time points to collect blood samples. Mice are sacrificed 72 hours after the final administration, and tissues (e.g., liver) are harvested. TTR mRNA levels in the liver are measured by qPCR, and plasma TTR protein levels are measured by ELISA to assess dose-dependent pharmacodynamic effects. |
| ADME/Pharmacokinetics |
Eplontersen is administered subcutaneously as a solution (45 mg in 0.8 mL) via single-use autoinjectors under the brand name Wainua. The usual dose regimen is 45 mg subcutaneously once per month. The compound is soluble in water at 100 mg/mL. As a powder, it is stable at -20°C for 3 years and at 4°C for 2 years; in solvent, it is stable at -80°C for 6 months and at -20°C for 1 month. It has a molecular weight of approximately 8606.50 g/mol. Eplontersen is metabolized to short sequences or individual nucleotides by plasma and intracellular nucleases and is not metabolized by P450 enzymes, resulting in no significant drug-drug interactions.
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| Toxicity/Toxicokinetics |
In the registration trial of eplontersen, liver test abnormalities occurred in 7.6% of treated patients, but elevations were mild, with no ALT elevations above 3 times the upper limit of normal (ULN) and no cases of jaundice. Common side effects can include vomiting, proteinuria, injection site reactions, and blurred vision. As TTR is a carrier for vitamin A, patients on eplontersen should take vitamin A supplements. Rare potential adverse events include vitamin A deficiency and embryofetal toxicity. The drug has been associated with minor liver test abnormalities but no instances of clinically apparent liver injury.
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| References |
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| Additional Infomation |
Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide that inhibits the production of human transthyretin (TTR) protein. It was developed by Ionis Pharmaceuticals and AstraZeneca and received its first approval in the USA on 21 December 2023 for ATTRv-PN. The drug is available as a 45 mg/0.8 mL solution for subcutaneous injection. It is also undergoing regulatory review in the EU, UK, Switzerland, and Canada for ATTRv-PN and is in Phase III development for ATTR cardiomyopathy. The NEURO-TTRansform Phase III trial demonstrated significant improvements in neuropathy impairment scores and quality of life measures.
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| CAS # |
1637600-16-8
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| Related CAS # |
2131025-75-5; 1637600-16-8
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| Sequence |
DNA, d([2′-O-(2-methoxyethyl)]m5rU-sp-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]rG-G-sp-T-sp-T-sp-A-sp-m5C-sp-A-sp-T-sp-G-sp-A-sp-A-sp-[2′-O-(2-methoxyethyl)]rA-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rC-sp-[2′-O-(2-methoxyethyl)]m5rC-sp-[2′-O-(2-methoxyethyl)]m5rC), 5′-[26-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-14,14-bis[[3-[[6-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]hexyl]amino]-3-oxopropoxy]methyl]-8,12,19-trioxo-16-oxa-7,13,20-triazahexacos-1-yl hydrogen phosphate]
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| Appearance |
Off-white to light yellow solid powder
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| Synonyms |
Wainua
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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 |
| 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
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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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