Ataluren

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H336：Kann Schläfrigkeit und Benommenheit verursachen.

  H373：Kann die Organe schädigen bei längerer oder wiederholter Exposition.

• Sicherheit

  P260：Dampf/Aerosol/Nebel nicht einatmen.

  P271：Nur im Freien oder in gut belüfteten Räumen verwenden.

  P314：Bei Unwohlsein ärztlichen Rat einholen / ärztliche Hilfe hinzuziehen.

  P403+P233：An einem gut belüfteten Ort aufbewahren. Behälter dicht verschlossen halten.

  P405：Unter Verschluss aufbewahren.

Ataluren Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Ataluren is a drug marketed under the trade name Translarna® which was developed by PTC Therapeutics and approved by the European Union in May 2014 for the treatment of Duchenne’s muscular dystrophy (DMD) and potentially other genetic disorders. Ataluren renders ribosomes less sensitive to premature stop or ‘read-through’ codons, which are thought to be beneficial in diseases such as DMD and cystic fibrosis.

• Beschreibung

  Nonsense mutations create a premature termination of mRNA translation and have been implicated in various genetic disorders, including muscular dystrophy and cystic fibrosis. PTC-124 is a nonaminoglycoside that has been reported to selectively induce ribosomes to read through premature nonsense stop signals on mRNA, thus allowing the production of full length, functional proteins. In a mouse model of cystic fibrosis caused by nonsense mutations, PTC-124 treatment (60 mg/kg s.c. injection or 0.3-0.9 mg/ml orally) has been shown to restore cystic fibrosis transmembrane conductance regulator (CFTR) protein expression and function. The target activity of PTC-124 was initially evaluated by firefly luciferase reporter cell-based nonsense codon assay (IC₅₀ = 7 nM); however, subsequent assessments using a Renilla reniformis luciferase reporter have failed to produce nonsense codon suppression activity. Thus, while PTC-124 is in clinical testing in patients with nonsense mutations within the CFTR or dystrophin genes, controversy surrounds its exact mechanism of action.

• Verwenden

  Nonsense mutations create a premature termination of mRNA translation and have been implicated in various genetic disorders, including muscular dystrophy and cystic fibrosis. PTC-124 is a nonaminoglycoside that has been reported to selectively induce ribosomes to read through premature nonsense stop signals on mRNA, thus allowing the production of full-length, functional proteins. In a mouse model of cystic fibrosis caused by nonsense mutations, PTC-124 treatment (60 mg/kg s.c. injection or 0.3-0.9 mg/ml orally) has been shown to restore cystic fibrosis transmembrane conductance regulator (CFTR) protein expression and function. The target activity of PTC-124 was initially evaluated by firefly luciferase reporter cell-based nonsense codon assay (IC50 = 7 nM); however, subsequent assessments using a Renilla reniformis luciferase reporter have failed to produce nonsense codon suppression activity. Thus, while PTC-124 is in clinical testing in patients with nonsense mutations within the CFTR or dystrophin genes, controversy surrounds its exact mechanism of action.[Cayman Chemical]

• Verwenden

  PTC-124 is a nonaminoglycoside that has been reported to induce ribosomes to read through premature nonsense stop signals on mRNA, allowing the production of full-length functional proteins,

• Definition

  ChEBI: 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid is a ring assembly and an oxadiazole.

• Trademarks

  Translarna?

• Mechanism of action

  The mechanism of action of Ataluren (PTC124) is to generate functionally normal myotonic dystrophy proteins by facilitating ribosomal read-through of nonsense mutations, thereby bypassing the pathogenic variant and continuing the translation process. Under normal conditions, ribosomes move along the mRNA that links amino acids into proteins until they reach the stop codon. When the ribosome encounters a premature termination codon (PTC) due to a nonsense mutation, eukaryotic release factors [eRF1 (green) and eRF3 (turquoise) complexed with GTP (yellow)] are recruited, and translation is terminated prematurely to produce the truncated protein. Ataluren is thought to interact with the ribosome to promote the recruitment of the proximity-recognition tRNAs, which in turn inhibits the nonsense mutation, allowing the PTC to be read through and synthesised. PTC to be read through and synthesise full-length proteins. The red amino acid on the near-recognition tRNA is incorporated into the read-through protein product. In the Ataluren-mediated nonsense repression model, the X on the tRNA indicates a mispairing at codon position three.
  

• Nebenwirkungen

  The most common side effects of Ataluren include: vomiting, diarrhoea, nausea, headache, loss of appetite, epigastric pain and flatulence. children between the ages of 2-5 years are prone to tiredness and weakness, fever, ear infections and rash. Other side effects that may occur are high triglyceride levels, high blood pressure, cough, nosebleeds, blood in the urine, and pain in the extremities. Most of the above adverse reactions are mild to moderate. No treatment-related serious adverse reactions have been reported in clinical studies. However, there have been patients who discontinued treatment due to constipation and incapacitating adverse reactions. Therefore, seek prompt medical attention if serious adverse reactions occur.

• Synthese

  The sequence to construct ataluren, which was described by the authors at PTC Therapeutics, commenced with commercially available methyl 3-cyanobenzoate (38). This ester was exposed to hydroxylamine in aqueous tert-butanol and warmed gently until the reaction was deemed complete. Then this mixture was treated with 2-fluorobenzoyl chloride dropwise and subsequently triethylamine dropwise. To minimize exotherm and undesired side products, careful control of the addition of reagents was achieved through slow dropwise addition of these liquid reagents. Upon complete consumption of starting materials and formation of amidooxime 39, the aqueous reaction mixture was then heated to 85 ?? to facilitate 1,2,4-oxadiazole formation, resulting in the tricyclic ester 40 in excellent yield across the three steps. Finally, saponification of ester 40 through the use of sodium hydroxide followed by acidic quench gave ataluren (V) in 96% over the two-step sequence.

  

• target

  CFTR

Ataluren Upstream-Materialien And Downstream Produkte

Ataluren Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(235)Suppliers

775304-57-9, Ataluren Verwandte Suche: