CAS 775304-57-9 Ataluren (HCID 11219835)

概要

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

名称と識別子

優先名称: Ataluren
IUPAC: 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid
現地名: アタルレン
英語名: Ataluren
分子式: C15H9FN2O3
分子量: 284.24

名称と別名

Ataluren775304-57-9PTC124PTC-1243-[5-(2-Fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoic acidTranslarnaK16AME9I3VAtalurenoDTXSID5046776Benzoic acid, 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]-DTXCID3026776

名称をさらに表示

アタルレン3-[5-(2-フルオロフェニル)-1,2,4-オキサジアゾール-3-イル]安息香酸CS-749AtalureAtarulonAtaluren, >=98%

Benzoic acid, 3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-atalurenumRefChem:560297M09AX03922-364-8Ataluren (PTC124)Ataluren [USAN]PTC 124

データベース識別子

CAS: 775304-57-9
PubChem CID: 11219835
DTXSID: DTXSID5046776
ChEMBL: CHEMBL256997
ChEBI: CHEBI:94805
UNII: K16AME9I3V
EC Number: 695-053-5、922-364-8
Nikkaji: J2.446.661B

物性

構造計算による物性

XLogP: 3.1
極性表面積: 76.2 Å²
水素結合供与体数: 1
水素結合受容体数: 6
回転可能結合数: 3
重原子数: 21
形式電荷: 0
複雑度: 382

実験および物理化学的性質

Drugs · 2 件

Pharmaceuticals -> Musculo-skeletal system -> Other drugs for disorders of the musculo-skeletal system

Pharmaceuticals -> Listed in ZINC15

物理化学的性質

融点: 241 · 241 - 242°C
沸点: 503.7 · 503.7±60.0 °C(Predicted)
比重(密度): 1.379 · 1.379
貯蔵温度: Refrigerator
溶解性: DMSO (わずかに)
外見: 白からオフホワイトの固体。
酸解離定数(Pka): 3.58 · 3.58±0.10(Predicted)
色: ホワイトからオフホワイト
InChI: InChI=1S/C15H9FN2O3/c16-12-7-2-1-6-11(12)14-17-13(18-21-14)9-4-3-5-10(8-9)15(19)20/h1-8H,(H,19,20)
InChIKey: OOUGLTULBSNHNF-UHFFFAOYSA-N
SMILES: C(O)(=O)C1=CC=CC(C2N=C(C3=CC=CC=C3F)ON=2)=C1
CAS データベース: 775304 · 775304-57-9

安全と法規制

GHS分類

GHS Classification · 3 件

This chemical does not meet GHS hazard criteria for 100% (2 of 2) of all reports.

Not Classified

Aggregated GHS information provided per 2 reports by companies from 1 notifications to the ECHA C&L Inventory.

危険有害性情報

Hazard Classes and CategoriesNot Classified

安全データ

wgk: WGK 3
hs_code: 2933998090
Hazard Classifications: STOT RE 2STOT SE 3
ストレージクラス: 11 - Combustible Solids

化学と産業

薬理情報

ATC Code · 2 件

M - Musculo-skeletal system

QM - Musculo-skeletal system

Protein BindingAtaluren is 99.6% bound to human plasma proteins and the binding is independent of plasma concentration. Ataluren does not distribute into red blood cells.

Mechanism of Action · 1 件

Ataluren enables ribosomal readthrough of mRNA containing premature stop codons that otherwise would result in premature termination of protein chains. Use of ataluren allows cellular machinery to bypass nonsense mutations in genetic material, continue the translation process, and thereby restore the production of a full-length, functional protein. The research on the effects of Ataluren on the translation and stability of nonsense-containing mRNA in vitor show that Ataluren promoted readthrough at each of the nonsense codons, showing maximal activity with UGA, while having no effect on mRNA levels. Unlike the stable cell line assays, Ataluren did not discriminate significantly between the UAG and UAA mRNAs. Ataluren was a more potent nonsense-suppressing agent than gentamicin, and exhibited 4- to 15-fold stimulation of in vitro readthrough relative to the controls at levels similar to those in the stable cell reporter assays. These results indicate that Ataluren modulates termination efficiency at premature nonsense codons.

Biological Half-LifeAtaluren plasma half-life ranges from 2-6 hours and is unaffected either by dose or repeated administration.

Metabolism/Metabolites · 1 件

Ataluren is metabolized by conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes, predominantly UGT1A9 in liver and intestine. In vivo, the only metabolite detected in plasma after oral administration of radio-labelled ataluren was the ataluren-O-1β-acyl glucuronide; exposure to this metabolite in humans was approximately 8% of the plasma AUC of ataluren.

Absorption, Distribution and Excretion · 2 件

Peak plasma levels of ataluren are attained approximately 1.5 hours after dosing in subjects who received medicinal product within 30 minutes of a meal.

After a single oral dose of radiolabeled ataluren, approximately half of the administered radioactive dose is recovered in the faeces and the remainder was recovered in the urine. In the urine, unchanged ataluren and the acyl glucuronide metabolite account for less than 1% and 49%, respectively, of the administered dose.

応用分野 · 2 件

説明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.

使用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]