775304-57-9

• 常用中文名：Ataluren (PTC124)
• 常用英文名：Ataluren (PTC124)
• CAS号：775304-57-9
• 分子式：C₁₅H₉FN₂O₃
• 分子量：284.242
• 相关类别： 生物化工 抑制剂 跨膜转运体(Transmembrane Transporters) CFTR 抑制剂
• 发布时间：2018-08-02 10:23:52
• 更新时间：2024-01-02 15:32:45
• Ataluren (PTC124) 是可口服的 CFTR-G542X 无义等位基因抑制剂。

名称

• 中文名: 3-[5-(2-氟苯基)-1,2,4-恶二唑-3-基]苯甲酸
• 英文名: 3-(5-(2-Fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoic acid
• 英文别名: 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid; Ataluren; Benzoic acid, 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]-; PTC124

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 503.7±60.0 °C at 760 mmHg
• 分子式: C₁₅H₉FN₂O₃
• 分子量: 284.242
• 闪点: 258.4±32.9 °C
• 精确质量: 284.059723
• PSA: 76.22000
• LogP: 3.73
• 蒸汽压: 0.0±1.4 mmHg at 25°C
• 折射率: 1.604
• 储存条件: 室温，干燥

生物活性

• 描述: Ataluren (PTC124) 是可口服的 CFTR-G542X 无义等位基因抑制剂。
• 相关类别:
  信号通路 >> 跨膜转运 >> CFTR
  研究领域 >> 代谢疾病
• 靶点:

  CFTR[1]

• 体外研究: 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]。
• 体内研究: 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]。
• 细胞实验: 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]。
• 动物实验: 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。
• 参考文献:

  [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.

MSDS

Material Safety Data Sheet Section1. Identification of the substance Product Name: Ataluren Synonyms: Section2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section3. Composition/information on ingredients. Ingredient name:Ataluren CAS number:775304-57-9 Section4. First aid measures Skin contact:Immediately wash skin with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. If irritation persists, seek medical attention. Eye contact:Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical attention. Inhalation:Remove to fresh air. In severe cases or if symptoms persist, seek medical attention. Ingestion:Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention. Section5. Fire fighting measures In the event of a fire involving this material, alone or in combination with other materials, use dry powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus should be worn. Section6. Accidental release measures Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national standards. Respiratory precaution:Wear approved mask/respirator Hand precaution:Wear suitable gloves/gauntlets Skin protection:Wear suitable protective clothing Eye protection:Wear suitable eye protection Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container for disposal. See section 12. Environmental precautions: Do not allow material to enter drains or water courses. Section7. Handling and storage Handling:This product should be handled only by, or under the close supervision of, those properly qualified in the handling and use of potentially hazardous chemicals, who should take into account the fire, health and chemical hazard data given on this sheet. Store in closed vessels, refrigerated. Storage: Section8. Exposure Controls / Personal protection Engineering Controls: Use only in a chemical fume hood. Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles. General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse. Section9. Physical and chemical properties Appearance:Not specified Boiling point:No data No data Melting point: Flash point:No data Density:No data Molecular formula:C15H9FN2O3 Molecular weight:284.2 Section10. Stability and reactivity Conditions to avoid: Heat, flames and sparks. Materials to avoid: Oxidizing agents. Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen fluoride. Section11. Toxicological information No data. Section12. Ecological information No data. Section13. Disposal consideration Arrange disposal as special waste, by licensed disposal company, in consultation with local waste disposal authority, in accordance with national and regional regulations. Section14. Transportation information Non-harzardous for air and ground transportation. Section15. Regulatory information No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302, or have known CAS numbers that exceed the threshold reporting levels established by SARA Title III, Section 313. SECTION 16 - ADDITIONAL INFORMATION N/A

安全

• 危害码 (欧洲): Xi
• 海关编码: 2934999090

合成路线

775304-60-4 ~95% 775304-57-9

文献：PTC THERAPEUTICS, INC. Patent: WO2007/117438 A2, 2007 ; Location in patent: Page/Page column 261 ;

393-52-2 ~78% 775304-57-9

文献：PTC THERAPEUTICS, INC. Patent: WO2008/30570 A1, 2008 ; Location in patent: Page/Page column 23-24 ;

1141475-82-2 393-52-2 ~% 775304-57-9

文献：Bioorganic and Medicinal Chemistry Letters, , vol. 24, # 11 p. 2473 - 2476

上下游产品

上游产品  3
775304-60-4 393-52-2 1141475-82-2
下游产品  0

海关

海关编码	2934999090
中文概述	2934999090. 其他杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%