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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- Pureté: 96.44%
- CAS No.: 1492984-65-2
- Masse moléculaire:7183.08
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Stockage:
-20°C, stored under nitrogen, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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.
Chemical Information
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CAS No. 1492984-65-2
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Appearance Solid
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Masse moléculaire 7183.08
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Color White to off-white
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SMILES
[Inotersen]
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Synonyms
GSK-2998728; ISIS-420915
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
-20°C, stored under nitrogen, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
Pureté et documentation
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Fiche technique (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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Instruction de manipulation (2242 KB)
Références
[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
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Inotersen Related Classifications
HY-112974 Related Classifications
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