Home Transmembrane Transporters CFTR inhibitor Ataluren (PTC124) For research use only.

Ataluren (PTC124)

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.

Ataluren (PTC124) Chemical Structure

Ataluren (PTC124) Chemical Structure

CAS No. 775304-57-9

Purity & Quality Control

Ataluren (PTC124) Related Products

Signaling Pathway

CFTR Signaling Pathways

CFTR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BAC_MMA∗EGFP Function Assay 20 μM 72 h  DMSO results in a significant increase in median peak fluorescence 23041189
Mut−/−MUTStop+/− Function Assay 20 μM 72 h  DMSO increases the amount of MUT mRNA 23041189
HEK293T Function Assay 10 µg/ml DMSO restores full-length harmonin a1 (∼80 kDa) in p.R31X-transfected cells 23027640
ML1 Function Assay 3.3/10 μM 48 h DMSO increases ARSB activity 22971959
ML2 Function Assay 3.3/10 μM 48 h DMSO increases ARSB activity 22971959
Click to View More Cell Line Experimental Data

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.
Features Demonstrates oral bioavailability, and an appropriate safety toxicology profile.
Targets
CFTR (nonsense mutant) [1]
(HEK293 cells)
In vitro
In vitro

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. 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
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. [2]
Animal Research Animal Models Cftr-/- hCFTR-G542X transgenic mice
Dosages ~60 mg/kg/day
Administration Subcutaneous injection or oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04336826 Completed
Nonsene Mutation Duchenne Muscular Dystrophy
PTC Therapeutics
 December 29 2021 Phase 2
NCT04014530 Recruiting
Colorectal Cancer|Endometrium Cancer
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|Merck Sharp & Dohme LLC|PTC Therapeutics
 August 1 2019 Phase 1|Phase 2
NCT02758626 Completed
Epilepsy
NYU Langone Health|PTC Therapeutics
 November 2016 Phase 2
NCT02819557 Completed
Duchenne Muscular Dystrophy
PTC Therapeutics
 June 9 2016 Phase 2
NCT02090959 Terminated
Muscular Dystrophy Duchenne|Muscular Dystrophies|Muscular Disorders Atrophic|Muscular Diseases|Musculoskeletal Diseases|Neuromuscular Diseases|Nervous System Diseases|Genetic Diseases X-Linked|Genetic Diseases Inborn
PTC Therapeutics
 March 20 2014 Phase 3
NCT01140451 Completed
Cystic Fibrosis
PTC Therapeutics|Cystic Fibrosis Foundation
 August 12 2010 Phase 3

Chemical Information & Solubility

Molecular Weight 284.24 Formula

C15H9FN2O3
CAS No. 775304-57-9 SDF Download Ataluren (PTC124) SDF
Smiles C1=CC=C(C(=C1)C2=NC(=NO2)C3=CC(=CC=C3)C(=O)O)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 57 mg/mL ( (200.53 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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