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PTC124

Cat. No. M1771
PTC124 Structure
Synonym:

Ataluren

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
10mM*1mL in DMSO USD 56  USD56 In stock
10mg USD 55  USD55 In stock
50mg USD 150  USD150 In stock
100mg USD 240  USD240 In stock
200mg USD 420  USD420 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

PTC124 (Ataluren) is a novel small molecular CFTR-G542X nonsense allele inhibitor. In safety pharmacology studies in rats and dogs, oral administration of PTC124 (Ataluren) induces no adverse neurological, pulmonary, or cardiovascular effects at doses through 1500 mg/kg. In toxicology studies in rats and dogs at oral doses through 1500 mg/kg for 28 days, PTC124 (Ataluren) has shown good tolerability. Both PTC124 doses were similarly active, improving total chloride transport with a combined mean change of -5.4 mV (p<0.001), and on-treatment responses (at least -5 mV improvement) and hyperpolarisations (values more electrically negative than -5 mV) in 61% (p<0.001) and 56% (p = 0.002) of patients. CFTR function was greater with time and was accompanied by trends toward improvements in pulmonary function and CF-related coughing. The high readthrough efficiency of PTC124 in combination with excellent biocompatibility makes it a promising therapeutic agent for PTCs in USH1C.

Customer Product Validations & Biological Datas
Source Mol Pharm (2014). Figure 4. PTC124
Method fluorescence microscopy
Cell Lines HeLa FLuc-opal cell
Concentrations 6, 9, and 12 μM
Incubation Time 72 h
Results After exposition of HeLa cells to 6 μM, 9 μM, and 12 μM PTC124 we observed the presence of green cells indicating that PTC124 induced the production of a full length functional H2B-GFP protein, despite the presence of a premature stop codon in its coding sequence, as evidenced by the clearly dose-dependent increase in the number of green cells.
Source Mol Pharm (2014). Figure 3. PTC124
Method luciferase activity assay
Cell Lines HeLa FLuc-opal cell
Concentrations 12 μM
Incubation Time 24 h
Results Following PTC124 exposition pFLuc190UGA transfected HeLa cells showed an increase of luciferase activity, this result is consistent with what previously published
Protocol
Cell Experiment
Cell lines Grip-Tite 293 cells transfected with the pFLuc190UGA construct
Preparation method Luciferase Reporter Assays. All cell-based assays were performed in 1,536-well plates with an assay volume of 4.5 μL per well. Comparative cell-based experiments were performed with cells from the same batch of transfected cells to control for transfection efficiency. Cells were incubated with compound or antibiotic for 16–72 h. In experiments with Grip-Tite cells, cells were washed with PBS before the addition of detection reagent containing the FLuc or RLuc substrate. Luminescence from luciferase activity was detected by using ViewLux (PerkinElmer). Experimental plates contained the transcriptional activator MS-275 as a positive control and DMSO-treated cells or mock-transfected cells as a negative control. Percentage activity was defined as the percentage signal above DMSO-treated cells.
Concentrations 0~100μM
Incubation time 24 hr
Animal Experiment
Animal models Cftr−/− hCFTR-G542X mice
Formulation saline
Dosages 15, 30 or 60mg/kg initiated 16 days after birth and continued once daily until the animals were killed
Administration Subcutaneous injections
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 284.24
Formula C15H9FN2O3
CAS Number 775304-57-9
Purity >99%
Solubility DMSO ≥47 mg/mL
Storage at -20°C
References

[1] Goldmann et al. Hum Gene Ther. PTC124-mediated translational readthrough of a nonsense mutation causing Usher syndrome type 1C.

[2] Wilschanski et al. Eur Respir J. Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis.

[3] Auld DS, et al. Proc Natl Acad Sci U S A. Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression.

[4] Du M, et al. Proc Natl Acad Sci U S A. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model.

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Keywords: PTC124, Ataluren supplier, CFTR, inhibitors

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