CAS:775304-57-9
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to off-white Solid
是CFTR-G542X 无义等位基因抑制剂。
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PTC124CAS:775304-57-9
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to off-white Solid
CAS | 775304-57-9 |
Chinese Name | 阿塔鲁伦 |
English Name | PTC124 |
Synonyms | Ataluren |
Molecular Formula | C15H9FN2O3 |
Molecular Weight | 284.24 |
Solubility | Soluble in DMSO |
Purity | ≥98% |
Appearance | White to off-white Solid |
Storage | Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
MDL | MFCD09864996 |
SMILES | O=C(C1=CC=CC(C2=NOC(C3=CC=CC=C3F)=N2)=C1)O |
Target Point | CFTR |
Passage | Membrane Transporter&Ion Channel |
Background | PTC124 is a CFTR-G542X nonsense allele inhibitor. |
Biological Activity | Ataluren是 CFTR-G542X 无义等位基因抑制剂。[1-3] |
In Vitro | 这种过早的“停止”信号(I类突变)阻止细胞产生全长CFTR蛋白[1]。 Ataluren(PTC124)- 一种新的化学实体,可选择性诱导早熟但非正常终止密码子的核糖体通读[2]。 |
In Vivo | Ataluren(PTC124)活性,使用含有无义酶的报告基因进行优化,促进表达肌营养不良蛋白无义等位基因的人和mdx小鼠的原代肌细胞中肌营养不良蛋白的产生,并在药物暴露后2-8周内在mdx小鼠中挽救横纹肌功能。 Ataluren(PTC124)在血浆暴露中对动物的耐受性基本上超过无义抑制所需的那些[2]。为了诱导无义抑制和增加PPT1酶活性,通过腹膜内(ip)注射给予2周龄雄性Cln1R151X小鼠的通读药物Ataluren(PTC124)。在原理证明研究中,这些治疗每天进行四次,连续2天。使用10 mg / kg时,Ataluren(PTC124)在肝脏中增加PPT1酶活性(通过非配对t检验P = 0.0001)和蛋白质水平(P = 0.0014,通过非配对t检验),但不增加PPT1酶活性或皮质中的蛋白质水平。这种组织特异性效应可能是由于Ataluren(PTC124)无法破坏血脑屏障(BBB),这降低了大脑中Ataluren(PTC124)的生物利用度,并阻止了Ataluren(PTC124)达到有效浓度在治疗窗内[3]。 |
Cell Experiment | 将含有LUC-190(UGA)的HEK293细胞的一式两份样品在5μMAtaluren(PTC124)(处理的)或1%DMSO(未处理)的存在下孵育20小时。收集细胞,在磷酸盐缓冲盐水(PBS)中洗涤两次,重悬于样品缓冲液(Bio-Rad)中并在干冰上运输至Kendrick Laboratories进行二维电泳分析等电聚焦(pH 3.5-10)在玻璃管,20,000 V小时。向每个样品中加入1μg原肌球蛋白内标。第二维SDS平板凝胶电泳在每个凝胶25mA下进行约6小时。电泳后,将凝胶转移到PVDF纸上。使用Phoretix软件的现场移动性的计算机化分析[2]。 |
Animal Experiment | 小鼠[3]将雄性小鼠随机分配到治疗组或媒介物对照组。每组6至8只小鼠用10或100mg / kg Ataluren(PTC124)溶解于含有DMSO的PBS(2%用于10mg / kg和20%用于100mg / kg)和(2-羟丙基)-β-环糊精(22%)经腹膜内(ip)注射,每日4次,连续2天。用药物载体处理六至八只对照小鼠:含有DMSO(2%或20%)和(2-羟丙基)-β-环糊精(22%)的PBS。在第二天最后一次注射后立即收集组织并在-80℃下储存以供进一步使用。 |
Data Literature Source | [1]. Pettit RS, et al. CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014 Jul; 39 (7) :500-11. [2]. Welch EM, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature, 2007, 447 (7140) , 87-91. [3]. Miller JN, et al. The novel Cln1 (R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy. Hum Mol Genet. 2015 Jan 1; 24 (1) :185-96. |
Unit | Piece |
Specification | 10mg 50mg |
是CFTR-G542X 无义等位基因抑制剂。