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Technical Data
| Formula | C15H9FN2O3 |
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| Molecular Weight | 284.24 | CAS No. | 775304-57-9 | |
| Solubility (25°C)* | In vitro | DMSO | 57 mg/mL (200.53 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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Biological Activity
| Description | Ataluren (PTC124) 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). Phase 3. | |
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| In vitro | Compared with Gentamicin which is only active at much higher concentrations, PTC124 is a more potent nonsense-suppressing agent and exhibits 4- to 15-fold stimulation of read-through relative to controls. PTC124 (0.01-3 μM) promotes dose-dependent read-through of all three nonsense codons in HEK293 cells harboring LUC-190 nonsense alleles with the highest read-through at UGA, followed by UAG and then UAA, but it does not suppress multiple proximal nonsense codons. Like Gentamicin, PTC124 is most active when a pyrimidine (in particular cytosine, C) follows the nonsense codon. Consistent with the stable cell line reporter assay, PTC124 (17 μM) promotes significant production of dystrophin in primary muscle cells from Duchenne muscular dystrophy (DMD) patients or MDXMDX mice expressing dystrophin nonsense alleles. PTC124 selectively promotes ribosomal read-through of premature termination but not normal termination codons, even at concentrations substantially greater than the values achieving maximal activity. [1] | |
| In vivo | Due to functional recovery of dystrophin production, oral, intraperitoneal or combined dosing of PTC124 for 2-8 weeks partially rescues functional strength deficit in dystrophic muscles of MDX mice, and results in partial protection against contraction-induced injury in the extensor digitorum longus (EDL) muscles, as well as significant reductions in serum creatine kinase values. [1] In Cftr-/- mice expressing a human CFTR-G542X transgene, subcutaneous or oral administration of PTC124 (~60 mg/kg) suppresses the G542X nonsense mutation in a dose-dependent manner, leading to a significant restoration of human (h)CFTR protein expression and function without any effect on nonsense-mediated mRNA decay (NMD) or other aspects of mRNA stability. PTC124 treatment (60 mg/kg) restores 29% of the normal intestinal transepithelial cAMP-stimulated shortcircuit currents observed in Cftr+/+ mice, displaying a significant advantage compared with Gentamicin. [2] | |
| Features | Demonstrates oral bioavailability, and an appropriate safety toxicology profile. |
Protocol (from reference)
| Animal Study:[2] |
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References
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Customer Product Validation
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Data from [Data independently produced by J Clin Invest, 2014, 124(1), 111-6]
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Data from [Data independently produced by Hum Mol Genet, 2014, 23(8), 2005-22]
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Data from [Data independently produced by Hum Mol Genet, 2014, 10.1093/hmg/ddu42]
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Data from [Data independently produced by Hum Mol Genet, 2014, 10.1093/hmg/ddu42]
Selleck's Ataluren (PTC124) has been cited by 47 publications
| Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis [ Stem Cell Reports, 2022, 17(10):2187-2202] | PubMed: 36084639 |
| Translational Read-Through Drugs (TRIDs) Are Able to Restore Protein Expression and Ciliogenesis in Fibroblasts of Patients with Retinitis Pigmentosa Caused by a Premature Termination Codon in FAM161A [ Int J Mol Sci, 2022, 23(7)3541] | PubMed: 35408898 |
| Novel Translational Read-through-Inducing Drugs as a Therapeutic Option for Shwachman-Diamond Syndrome [ Biomedicines, 2022, 10(4)886] | PubMed: 35453634 |
| Translational readthrough of ciliopathy genes BBS2 and ALMS1 restores protein, ciliogenesis and function in patient fibroblasts [ EBioMedicine, 2021, 70:103515] | PubMed: 34365092 |
| Präklinische ex vivo-Effekte von CFTR-Modulatoren an humanen Rektumbiopsien zur Medikamentenentwicklung bei Mukoviszidose [ Universitätsmedizin Berlin, 2021, 10.17169/refubium-29871] | PubMed: None |
| Pharmacological premature termination codon readthrough of ABCB11 in bile salt export pump deficiency: an in vitro study [ Hepatology, 2020, 10.1002/hep.31476] | PubMed: 32702170 |
| Loss of N-Glycanase 1 Alters Transcriptional and Translational Regulation in K562 Cell Lines [ G3 (Bethesda), 2020, 4;10(5):1585-1597] | PubMed: 32265286 |
| Nonsense suppression induced readthrough of a novel PAX6 mutation in patient-derived cells of congenital aniridia. [ Mol Genet Genomic Med, 2020, 10.1002/mgg3.1198] | PubMed: 32125788 |
| CRISPR-Pass: Gene Rescue of Nonsense Mutations Using Adenine Base Editors. [ Mol Ther, 2019, 27(8):1364-1371] | PubMed: 31164261 |
| Variable readthrough responsiveness of nonsense mutations in hemophilia A [ Haematologica, 2019, 10.3324/haematol.2018.212118] | PubMed: 31197069 |
RETURN POLICY
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.