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My Cart> Small Molecule Compounds > Inhibitors & Antagonists & Agonists > Membrane Transporter & Ion Channel > PTC124CAS：775304-57-9
Molecular Formula：C15H9FN2O3
Molecular Weight：284.24
Storage：Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year
Purity：≥98%
Appearance：White to off-white Solid
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| CAS | 775304-57-9 |
| Name | PTC124 |
| 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。
Remark：These protocols are for reference only. Solarbio does not independently validate these methods.
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