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Ataluren
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Ataluren图片
CAS NO:775304-57-9
包装与价格:
包装价格(元)
5 mg电议
10 mg电议
50 mg电议
100 mg电议
200 mg电议

产品名称
PTC124
产品介绍
Ataluren 是一种可口服的CFTR-G542X无义等位基因抑制剂。

产品描述

Ataluren is a novel, orally administered drug that targets nonsense mutations. Ataluren is approved for use by the European Medicines Agency to treat Duchenne Muscular Dystrophy in patients aged 5 years and older who are able to walk.

体外活性

在表达人CFTR-G542X转基因的Cftr -/- 小鼠中,皮下或口服给予PTC124(?60 mg/kg),以剂量依赖性方式抑制G542X无义突变,导致人 (h)CFTR蛋白的表达和功能的明显恢复,对无义介导的mRNA降解(NMD)或mRNA稳定性的其他方面没有任何影响.60 mg/kg PTC124处理Cftr+/+小鼠,观察到正常肠道跨上皮cAMP刺激的短路电流恢复29%,与庆大霉素相比具有的明显优势.

体内活性

0.01-3 μM PTC124促进含有LUC-190无义等位基因的HEK293细胞中所有三个无义密码子的剂量依赖性通读,UGA读数最高,其次是UAG,然后是UAA,但它不抑制多重近端无义密码子。17 μM PTC124与稳定细胞系报告实验测定一致,PTC124(17 μM)促进Duchenne型肌营养不良症(DMD)患者或表达肌营养不良蛋白酶无义等位基因的MDXMDX小鼠的原代肌细胞中肌养蛋白的显著生成。PTC124选择性促进核糖体提前终止密码子而非正常终止密码子的通读,即使浓度大大高于达到最大活性所需值。与仅在更高浓度下有活性的庆大霉素相比,PTC124是更有效的无义抑制剂,并且相对于对照显示4至15倍通读刺激。PTC124与庆大霉素相似,在无义密码子后的嘧啶处(尤其是胞嘧啶,C) 活性最高。

细胞实验

PTC124 (Ataluren) is prepared in DMSO and stored, and then diluted with appropriate medium (DMSO 1%) before use[2]. Duplicate samples of HEK293 cells harbouring LUC-190 (UGA) are incubated in the presence of 5?μM PTC124 (treated) or 1% DMSO (untreated) for 20?h. The cells are collected, washed twice in phosphate buffered saline (PBS), resuspended in sample buffer (Bio-Rad) and shipped on dry ice to Kendrick Laboratories for two-dimensional electrophoretic analysis Isoelectric focusing (pH?3.5-10) is carried out in glass tubes for 20,000 V-hours. One?μg of a tropomyosin internal standard is added to each sample. Second dimension SDS slab gel electrophoresis is carried out for approximately 6?h at 25?mA per gel. After electrophoresis, gels are transferred to PVDF paper. Computerized analysis of spot mobility used Phoretix software[2].

Cas No.

775304-57-9

分子式

C15H9FN2O3

分子量

284.246

别名

PTC124

储存和溶解度

Ethanol:<1 mgml
DMSO:53 mg/mL (186.5 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years