Eteplirsen
Based on 1 Customer Validation
Eteplirsen (AVI 4658) is a phosphorylated diamine morpholino oligonucleotide that targets exon 51 of the human Duchenne muscular dystrophy (DMD) gene. Eteplirsen induces exon 51 skipping, causing it to be skipped during splicing, thereby restoring the translation reading frame and producing a shortened functional dystrophin. Eteplirsen can be used in research on Duchenne muscular dystrophy.
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- 純度: 98.50%
- CAS 番号: 1173755-55-9
- 分子式: C364H569N177O122P30
- 分子量:10305.74
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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
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溶剤 & 溶解度
- 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
Eteplirsen (AVI 4658) (100 nM; 24 h) 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) induces exon 51 skipping in differentiated human rhabdomyosarcoma (RD) cells[4].
Eteplirsen (100 nM; 24 h) 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.
Eteplirsen (up to 320 mg/kg; i.v. or s.c.; once weekly for 12 weeks) 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) 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) 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.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
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CAS 番号 1173755-55-9
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性状 Solid
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分子量 10305.74
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分子式 C364H569N177O122P30
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Color White to off-white
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SMILES
O=C1NC(N)=NC2=C1N=CN2[C@H]3CNC[C@H](O3)COP(N4C[C@H](O[C@@H](N5C(N=CN=C6N)=C6N=C5)C4)COP(N7C[C@@H](COP(N8C[C@@H](COP(N9C[C@@H](COP(N%10C[C@@H](COP(N%11C[C@@H](COP(N%12C[C@@H](COP(N%13C[C@@H](COP(N%14C[C@@H](COP(N%15C[C@@H](COP(N%16C[C@@H](COP(N%17C[C@@H](COP(N%18C[C@@H](COP(N%19C[C@@H](COP(N%20C[C@@H](COP(N%21C[C@@H](COP(N%22C[C@@H](COP(N%23C[C@@H](COP(N%24C[C@@H](COP(N%25C[C@@H](COP(N%26C[C@@H](COP(N%27C[C@@H](COP(N%28C[C@@H](COP(N%29C[C@@H](COP(N%30C[C@@H](COP(N%31C[C@@H](COP(N%32C[C@@H](COP(N%33C[C@@H](COP(N%34C[C@@H](COP(N%35CCN(C(OCCOCCOCCO)=O)CC%35)(N(C)C)=O)O[C@@H](N%36C(N=C(N)C=C%36)=O)C%34)(N(C)C)=O)O[C@@H](N%37C(NC(C(C)=C%37)=O)=O)C%33)(N(C)C)=O)O[C@@H](N%38C(N=C(N)C=C%38)=O)C%32)(N(C)C)=O)O[C@@H](N%39C(N=C(N)C=C%39)=O)C%31)(N(C)C)=O)O[C@@H](N%40C(N=CN=C%41N)=C%41N=C%40)C%30)(N(C)C)=O)O[C@@H](N%42C(N=CN=C%43N)=C%43N=C%42)C%29)(N(C)C)=O)O[C@@H](N%44C(N=C(N)C=C%44)=O)C%28)(N(C)C)=O)O[C@@H](N%45C(N=CN=C%46N)=C%46N=C%45)C%27)(N(C)C)=O)O[C@@H](N%47C(NC(C(C)=C%47)=O)=O)C%26)(N(C)C)=O)O[C@@H](N%48C(N=C(N)C=C%48)=O)C%25)(N(C)C)=O)O[C@@H](N%49C(N=CN=C%50N)=C%50N=C%49)C%24)(N(C)C)=O)O[C@@H](N%51C(N=CN=C%52N)=C%52N=C%51)C%23)(N(C)C)=O)O[C@@H](N%53C(N=C(N)NC%54=O)=C%54N=C%53)C%22)(N(C)C)=O)O[C@@H](N%55C(N=C(N)NC%56=O)=C%56N=C%55)C%21)(N(C)C)=O)O[C@@H](N%57C(N=CN=C%58N)=C%58N=C%57)C%20)(N(C)C)=O)O[C@@H](N%59C(N=CN=C%60N)=C%60N=C%59)C%19)(N(C)C)=O)O[C@@H](N%61C(N=C(N)NC%62=O)=C%62N=C%61)C%18)(N(C)C)=O)O[C@@H](N%63C(N=CN=C%64N)=C%64N=C%63)C%17)(N(C)C)=O)O[C@@H](N%65C(NC(C(C)=C%65)=O)=O)C%16)(N(C)C)=O)O[C@@H](N%66C(N=C(N)NC%67=O)=C%67N=C%66)C%15)(N(C)C)=O)O[C@@H](N%68C(N=C(N)NC%69=O)=C%69N=C%68)C%14)(N(C)C)=O)O[C@@H](N%70C(N=C(N)C=C%70)=O)C%13)(N(C)C)=O)O[C@@H](N%71C%72=C(N=C%71)C(N)=NC=N%72)C%12)(N(C)C)=O)O[C@@H](N%73C(NC(C(C)=C%73)=O)=O)C%11)(N(C)C)=O)O[C@@H](N%74C(NC(C(C)=C%74)=O)=O)C%10)(N(C)C)=O)O[C@@H](N%75C(NC(C(C)=C%75)=O)=O)C9)(N(C)C)=O)O[C@@H](N%76C(N=C(N)C=C%76)=O)C8)(N(C)C)=O)O[C@@H](N%77C(NC(C(C)=C%77)=O)=O)C7)(N(C)C)=O)(N(C)C)=O
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別名
AVI 4658
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配列
RNA, [P-deoxy-P-(dimethylamino)](2',3'-dideoxy-2',3'-imino-2',3'-seco)(2'a→5')(C-m5U-C-C-A-A-C-A-m5U-C-A-A-G-G-A-A-G-A-m5U-G-G-C-A-m5U-m5U-m5U-C-m5U-A-G), 5'-[P-[4-[[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]carbonyl]-1-piperazinyl]-N,N-dimethylphosphonamidate]
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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)
溶剤 & 溶解度
DMSO : 50 mg/mL (4.85 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1.25 mg/mL (0.12 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 1.25 mg/mL (0.12 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 33.33 mg/mL (3.23 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
純度とドキュメンテーション
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データシート (278 KB)
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SDS (254 KB)
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- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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取扱説明書 (2242 KB)
参考文献
[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]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.0970 mL | 0.4852 mL | 0.9703 mL | 2.4258 mL |
Eteplirsen 関連分類
HY-108753 関連分類
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