Eteplirsen sodium
Based on 1 Customer Validation
Eteplirsen (AVI 4658) sodium is a phosphorylated diamine morpholino oligonucleotide that targets exon 51 of the human Duchenne muscular dystrophy (DMD) gene. Eteplirsen sodium induces exon 51 skipping, causing it to be skipped during splicing, thereby restoring the translation reading frame and producing a shortened functional dystrophin. Eteplirsen sodium can be used in research on Duchenne muscular dystrophy.
For research use only. We do not sell to patients.
- Purity: 91.16%
- Formula: C364H539N177Na30O122P30
- Molecular Weight:10306 (free acid)
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Storage:
-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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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Eteplirsen (AVI 4658) (100 nM; 24 h) sodium induces exon 51 skipping in the tri-chromatic reporter cell line (Flp-In CHO cells harboring the DMD exon 51 minigene)[4].
Eteplirsen (10 µM; 24 h) sodium induces exon 51 skipping in differentiated human rhabdomyosarcoma (RD) cells[4].
Eteplirsen (100 nM; 24 h) sodium promotes exon 51 skipping in the tri-chromatic reporter cell line, leads to the expression of TagRFP-conjugated proteins as a readout of successful splicing modulation[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Flp-In CHO cells harboring DMD exon 51 minigene
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Concentration:100 nM
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Incubation Time:24 h
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Result:Induced exon 51 skipping.
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Cell Line:Differentiated human rhabdomyosarcoma (RD) cells
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Concentration:10 µM
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Incubation Time:24 h
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Result:Induced exon 51 skipping in endogenous DMD transcript.
| Species | Dose | Route | Note | AUC0-last | CL | Cmax | T1/2 | Vss | Tmax | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|---|
| Cynomolgus Monkey[2] | 320 mg/kg | i.v. | Day 1 | 1550 μg·h/mL | 3.56 mL/min/kg | 1340 μg/mL | 3.92 h | 610 mL/kg | / | / |
| Cynomolgus Monkey[2] | 320 mg/kg | i.v. | Day 71 | 1020 μg·h/mL | 6.68 mL/min/kg | 846 μg/mL | 3.51 h | 1100 mL/kg | / | / |
| Cynomolgus Monkey[2] | 320 mg/kg | s.c. | Day 1 | 1620 μg·h/mL | / | 77.6 ng/mL | 7.0 h | / | 7.3 h | 104 % |
| Cynomolgus Monkey[2] | 320 mg/kg | s.c. | Day 71 | 1250 μg·h/mL | / | 57 ng/mL | 8.6 h | / | 9.3 h | 122 % |
| Cynomolgus Monkey[2] | 40 mg/kg | i.v. | Day 1 | 162 μg·h/mL | 4.33 mL/min/kg | 196 μg/mL | 3.24 h | 392 mL/kg | / | / |
| Cynomolgus Monkey[2] | 40 mg/kg | i.v. | Day 71 | 143 μg·h/mL | 4.97 L/min/kg | 192 μg/mL | 3.13 h | 444 mL/kg | / | / |
| Cynomolgus Monkey[2] | 5 mg/kg | i.v. | Day 1 | 17.1 μg·h/mL | 5.05 mL/min/kg | 21.6 μg/mL | 1.59 h | 397 mL/kg | / | / |
| Cynomolgus Monkey[2] | 5 mg/kg | i.v. | Day 71 | 14.4 μg·h/mL | 6.19 mL/min/kg | 21.5 μg/mL | 1.8 h | 469 mL/kg | / | / |
Eteplirsen (up to 320 mg/kg; i.v. or s.c.; once weekly for 12 weeks) sodium induces dose-dependent microscopic renal effects in cynomolgus monkeys, including basophilic granules (minimal), basophilic tubules (minimal to moderate), and tubular vacuolation (minimal to mild), Eteplirsen (AVI 4658) sodium-induced renal effects are reversible after a 28-day recovery period [2].
Eteplirsen (up to 320 mg/kg; i.v.; single dose or up to 320 mg/kg; s.c.; once weekly for 4 weeks) sodium exhibits no test article-related effects on cardiovascular, respiratory, global neurological, renal, or liver parameters in cynomolgus monkeys at the maximum feasible dose[3].
Eteplirsen (up to 2000 mg/kg; i.v.; single dose) sodium shows no mutagenic potential in the mouse bone marrow erythrocyte micronucleus test[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Repeat-dose toxicity study in cynomolgus monkeys (Chinese origin, 2.7-3 years old)[2]
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Dosage:0, 5, 40, 320 mg/kg
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Administration:i.v. or s.c.; once weekly for 12 weeks
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Result:Showed no drug-related effects on survival, clinical observations, body weight, food consumption, ophthalmoscopic or electrocardiographic evaluations, hematology, clinical chemistry, urinalysis, organ weights, or macroscopic evaluations.
Exhibited dose-dependent microscopic renal effects: basophilic granules (minimal), basophilic tubules (minimal to moderate), tubular vacuolation (minimal to mild); findings were partially reversible after 28-day recovery.
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Animal Model:Safety pharmacology evaluation in male cynomolgus monkeys[3]
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Dosage:0, 40, 160, 320 mg/kg
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Administration:i.v. or s.c.; single dose
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Result:Showed no test article-related effects on cardiovascular (arterial blood pressure, heart rate, ECG), respiratory (respiratory rate, inspiratory/expiratory time, tidal volume), global neurological, renal, or liver parameters at doses up to 320 mg/kg.
Chemical Information
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Appearance Solid
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Molecular Weight 10306 (free acid)
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Formula C364H539N177Na30O122P30
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Color White to off-white
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SMILES
[Eteplirsen (sodium)]
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Synonyms
AVI 4658 sodium
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, stored under nitrogen, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
Purity & Documentation
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Data Sheet (270 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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Handling Instructions (2242 KB)
References
[1]. Lim KR, et al. Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Des Devel Ther. 2017 Feb 28;11:533-545. [Content Brief]
[2]. Sazani P, et al. Repeat-dose toxicology evaluation in cynomolgus monkeys of AVI-4658, a phosphorodiamidate morpholino oligomer (PMO) drug for the treatment of duchenne muscular dystrophy. Int J Toxicol. 2011 May;30(3):313-21. [Content Brief]
[3]. Sazani P, et al. Safety pharmacology and genotoxicity evaluation of AVI-4658. Int J Toxicol. 2010 Mar-Apr;29(2):143-56. [Content Brief]
[4]. Shimo T, et al. Construction of a tri-chromatic reporter cell line for the rapid and simple screening of splice-switching oligonucleotides targeting DMD exon 51 using high content screening. PLoS One. 2018 May 16;13(5):e0197373. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Eteplirsen sodium Related Classifications
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