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Purity: ≥98%
Ataluren (formerly known as PTC 124; PTC-124; PTC124; trade name Translarna) is a novel, potent and orally bioavailable CFTR-G542X nonsense allele inhibitor that has been approved as a medication for the treatment of Duchenne muscular dystrophy. It selectively induces ribosomal read-through of premature but not normal termination codons with EC50 of 0.1 μM in HEK293 cells, may provide treatment for genetic disorders caused by nonsense mutations (e.g. CF caused by CFTR nonsense mutation). Ataluren is currently being investigated for use in patients with nonsense mutation Duchenne/Becker muscular dystrophy (nmDBMD) and cystic fibrosis (nmCF).
| ln Vitro |
This premature “stop” signal (a class I mutation) stops the cell from manufacturing a full-length CFTR protein[1]. Ataluren (PTC124)-a novel chemical entity that selectively stimulates ribosomal readthrough of premature but not normal termination codons[2].
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| ln Vivo |
After 2–8 weeks of medication exposure, ataluren (PTC124) activity, which was optimized using nonsense-containing reporters, rescues striated muscle function in mdx mice and increases the production of dystrophin in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles. In animals, ataluren (PTC124) is well tolerated at plasma exposures significantly higher than those needed for nonsense suppression[2]. Male Cln1R151X mice are injected intraperitoneally (ip) with the read-through drug Ataluren (PTC124) at two months of age in order to increase PPT1 enzyme activity and induce nonsense suppression. In a proof-of-principle study, these treatments are given four times a day for two days in a row. When Ataluren (PTC124) was used at a dose of 10 mg/kg, it was found to increase PPT1 enzyme activity (P=0.0001 by unpaired t-test) and protein level (P=0.0014 by unpaired t-test) in the liver, but not in the cortex. The probable cause of this tissue-specific effect is Ataluren (PTC124)'s incapacity to cross the blood brain barrier (BBB), which reduced the drug's bioavailability in the brain and kept it from building up to an effective concentration during the therapeutic window[3].
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| Animal Protocol |
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| References |
[1]. Pettit RS, et al. CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014 Jul;39(7):500-11.
[2]. Welch EM, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature, 2007, 447(7140), 87-91. [3]. Miller JN, et al. The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy. Hum Mol Genet. 2015 Jan 1;24(1):185-96 |
| Molecular Formula |
C15H9FN2O3
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| Molecular Weight |
284.24
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| CAS # |
775304-57-9
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| Related CAS # |
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| SMILES |
O=C(C1=CC=CC(C2=NOC(C3=CC=CC=C3F)=N2)=C1)O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.80 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: (saturation unknown) in 1% DMSO +30% polyethylene glycol+1% Tween 80 : 30mg/mL (add these co-solvents sequentially from left to right, and one by one), |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5182 mL | 17.5908 mL | 35.1815 mL | |
| 5 mM | 0.7036 mL | 3.5182 mL | 7.0363 mL | |
| 10 mM | 0.3518 mL | 1.7591 mL | 3.5182 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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