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Ataluren (PTC124)

Ataluren (PTC124)

Item no.	S6003-10
Manufacturer	Selleckchem
CASRN	775304-57-9
Amount	10 mg
Category	Food Safety Antibiotics Neuroscience Protein Aggregation, Clearance & Misfolding Inhibitors & Compound Libraries Small Molecules
Type	Inhibitors
Specific against	other
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	Nonsense mutation;Others
Similar products	PTC124
Available
Administration	Subcutaneous injection or oral administration
Animal Models	Cftr-/- hCFTR-G542X transgenic mice
Chemical Name	3-(5-(2-fluorophenyl)-1, 2, 4-oxadiazol-3-yl)benzoic acid
Clinical Trials	A Phase III study of PTC124 for previously treated patients with nonsense mutation dystrophinopathy (nmDBMD) in Europe, Israel, Australia, and Canada is currently ongoing.
Description	PTC124 (Ataluren) is a potent nonsense mutation inhibitor with EC50 of ca.0.1 uM.
Dosages	ca.60 mg/kg/day
Features	PTC124 demonstrates oral bioavailability, and an appropriate safety toxicology profile.
Formulation	Dissolved in DMSO, and diluted in saline
IC50	ca.0.1 uM [1], ca.0.1 uM [1], ca.0.1 uM [1], ca.0.1 uM [1], ca.0.1 uM [1], ca.0.1 uM [1]
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 uM) 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 uM) 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 (ca.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]
Kinase Assay	Assays for read-through of LUC premature termination codons, Stock solutions of PTC124 (6 mM) are prepared in 100% DMSO HEK293 cells grown in a medium containing fetal bovine serum (FBS) and are stably transfected with LUC genes containing premature terminators at codon 190 (and 11 contextual variants thereof), treated with increasing concentrations of PTC124 for 16 hours, and assayed for luciferase activity. Luminescence of each culture relative to the control is quantified by standard procedures using a Viewlux CCD imager. Luminescence data are normalized to that produced with DMSO, and the fold suppression over background is calculated as (PTC124light units/DMSOlight units).
Molecular Weight (MW)	284, 24
Picture ChemicalStructure Description	PTC124 (Ataluren) Chemical Structure
Picture Description 1	, , Dr Lu Tan of Childrens Hospital of Philadelphia, PTC124 (Ataluren)purchased from Selleck, Quantitative RT-PCR analysis of CPT1A in normal and patient fibroblasts treated with various concentration of PTC124 (0, 1, 3 and 5 M) for 72 hours. The relative contents of mRNA were calculated by using the Ct method. Expression was normalized to human GAPDH and no significant fold difference was observed in the patient mRNA levels after treatment with PTC124. The normal control cells showed approximately 10-fold higher expression than patient cells. Data are presented as mean, Error bar indicates SEM
Solubility (25C)	DMSO 57 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Storage	2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

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Amount: 10 mg

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