Inotersen
Based on 1 Customer Validation
Inotersen (GSK-2998728; ISIS-420915) is a 2'-O-methoxyethyl-modified antisense oligonucleotide and transthyretin (TTR) inhibitor with low genotoxicity. Inotersen triggers RNase H1-mediated degradation by binding to TTR mRNA, thereby effectively reducing the production of both mutant and wild-type transthyretin in the liver. Inotersen significantly reduces amyloid fiber deposition, yet specific toxicities such as inflammation or tumors are observed at high doses in some animal models. Inotersen is used in studies of hereditary transthyretin amyloidosis and the associated polyneuropathy and cardiomyopathy.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 96.44%
- CAS 番号: 1492984-65-2
- 分子量:7183.08
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保管条件:
-20°C, stored under nitrogen, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
Inotersen inhibits the production of TTR in human hepatocellular carcinoma HepG2 cells in in vitro screening assays[1].
Inotersen specifically and selectively detects anti-Inotersen antibodies in human plasma, with a sensitivity of 6.28 ng/mL, and exhibits strong drug tolerance. It can still recognize 100 ng/mL of anti-Inotersen antibodies even in the presence of 16.0 μg/mL of circulating Inotersen[2].
Inotersen (10-1000 nM; 48 h) dose-dependently reduces the mRNA and protein levels of transthyretin (TTR) in the human hepatocellular carcinoma cell line HepG2[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2, HepaRG
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Concentration:0 nM, 10 nM, 100 nM, 1000 nM
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Incubation Time:48 h
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Result:Dose-dependent reduced transthyretin (TTR) mRNA and protein levels:
At 10 nM, TTR mRNA decreased by approximately 20%, at 100 nM by approximately 50%, and at 1000 nM by approximately 75%, with protein levels showing a similar decreasing trend.
Inotersen (>40 mg/kg/week; 3-6 months) causes mild to moderate mononuclear cell infiltration in the hepatic sinusoids, lymph nodes and injection sites of mice after 3 and 6 months of administration, with no adverse effects on the overall health of the mice[1].
Inotersen (10-80 mg/kg/w; s.c.; once weekly; 26 weeks) induces mild, dose-dependent changes in serum biochemical parameters and typical microscopic effects in Tg.rasH2 mice[5].
Subcutaneous administration of Inotersen (0.5-6 mg/kg/w; s.c.; once weekly; 2 years) to Sprague-Dawley rats for up to 2 years induces dose-dependent non-neoplastic effects and subcutaneous fibrosarcomas at injection sites[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Macaca fascicularis (male and female)[1]
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Dosage:3 mg/kg; 6 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:s.c.; days 1, 3, 5, 7 then once weekly; up to 39 weeks
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Result:Reported ADA incidence rates of 28.6% for 3 mg/kg, 50.0% for 6 mg/kg, 42.9% for 10 mg/kg, and 44.4% for 20 mg/kg.
Reported median ADA onset of 140 days for 3 mg/kg, 185 days for 6 mg/kg, 185 days for 10 mg/kg, and 140 days for 20 mg/kg.
Reported median peak titers of 1600 for 3 mg/kg, 800 for 6 mg/kg, 200 for 10 mg/kg, and 300 for 20 mg/kg (all including minimum required dilution of 50).
Observed elevated plasma trough inotersen concentrations in ADA-positive monkeys compared to ADA-negative monkeys, but no consistent differences in liver or kidney inotersen concentrations, liver TTR mRNA levels, or plasma TTR protein levels.
Observed no differences in complement C3 levels or platelet counts between ADA-positive and ADA-negative monkeys across any dose or treatment duration.
化学情報
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CAS 番号 1492984-65-2
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性状 Solid
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分子量 7183.08
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Color White to off-white
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SMILES
[Inotersen]
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別名
GSK-2998728; ISIS-420915
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
-20°C, stored under nitrogen, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
純度とドキュメンテーション
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データシート (272 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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取扱説明書 (2242 KB)
参考文献
[1]. Mathew V, et al. Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis. Drug Des Devel Ther. 2019;13:1515-1525. Published 2019 May 6. [Content Brief]
[2]. Yu RZ, et al. Immunogenicity Assessment of Inotersen, a 2'-O-(2-Methoxyethyl) Antisense Oligonucleotide in Animals and Humans: Effect on Pharmacokinetics, Pharmacodynamics, and Safety. Nucleic Acid Ther. 2020;30(5):265-275. [Content Brief]
[4]. Kim TW, et al. Carcinogenicity assessment of inotersen in Tg.rasH2 mice and Sprague-Dawley rats: Implications for 2'-MOE antisense oligonucleotides. Regul Toxicol Pharmacol. 2025;155:105743. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Inotersen 関連分類
HY-112974 関連分類
Powered by Bioz
- Inotersen
- 1492984-65-2
- GSK-2998728
- ISIS-420915
- GSK2998728
- GSK 2998728
- ISIS420915
- ISIS 420915
- ISIS-420915
- Transthyretin (TTR)
- Tg.rasH2 mice
- cynomolgus monkeys
- human TTR Ile84Ser transgenic mice
- transthyretin (TTR)
- CD-1 mice
- human hepatoma HepG2 cells
- Sprague Dawley rats
- hereditary transthyretin amyloidosis
- human TTR mRNA
- RNase H1
- Inhibitor
- inhibitor
- inhibit