Ataluren

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.

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]

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.

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.

Ataluren Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte

Ataluren Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Firmenname	Telefon	E-Mail	Land	Produktkatalog	Edge Rate
Shanghai Famo Biotech Co Ltd	+86-36680037 +86-18550473860	mayan@famobiotech.com;sales@famobiotech.com	China	528	58
shandong perfect biotechnology co.ltd	+86-53169958659; +8618596095638	sales@sdperfect.com	China	294	58
Henan Bao Enluo International TradeCo.，LTD	+86-17331933971 +86-17331933971	deasea125996@gmail.com	China	2503	58
Hangzhou ICH Biofarm Co., Ltd	+86-0571-28186870; +undefined8613073685410	sales@ichemie.com	China	990	58
Anhui Ruihan Technology Co., Ltd	+8617756083858	daisy@anhuiruihan.com	China	994	58
HEBEI SHENGSUAN CHEMICAL INDUSTRY CO.,LTD	+8615383190639	admin@86-ss.com	China	1000	58
Capot Chemical Co.,Ltd.	571-85586718 +8613336195806	sales@capotchem.com	China	29798	60
ATK CHEMICAL COMPANY LIMITED	+undefined-21-51877795	ivan@atkchemical.com	China	32836	60
career henan chemical co	+86-0371-86658258 +8613203830695	sales@coreychem.com	China	29888	58
Biochempartner	0086-13720134139	candy@biochempartner.com	CHINA	967	58

775304-57-9()Verwandte Suche:

---

• Ptc-124
• PTC-124,ataluren
• Ataluren (PTC124)
• Ataluren PTC 124 Ataluren
• Ataluren, >=98%
• PTC124, 775304-57-9
• 3-[5-(2-Fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid
• Ataluren [usan]
• Benzoic acid, 3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-
• Ptc 124
• Atarulon
• CS-749
• ATALUREN;PTC-124;PTC 124
• Ataluren (PTC124) USP/EP/BP
• Ptc124
• Ataluren
• 4H-1-Benzopyran-4-one,6-bromo-2,3-dihydro-2,7-dimethyl-
• Estr-4-en-3-one,17-hydroxy-,(21β)-
• 775304-57-9
• C15H9FN2O3
• Inhibitors
• Ribosome binding agent
• API