1337531-36-8

• 常用中文名：GSK2606414
• 常用英文名：GSK2606414
• CAS号：1337531-36-8
• 分子式：C₂₄H₂₀F₃N₅O
• 分子量：451.444
• 相关类别： 生物化工 抑制剂 细胞凋亡(Apoptosis) PERK 抑制剂
• 发布时间：2017-12-11 18:43:44
• 更新时间：2024-01-04 19:35:39
• GSK2606414 是一种具有选择性的，可口服的 PERK 抑制剂，IC₅₀ 值为 0.4 nM。

名称

• 中文名: 7-甲基-5-[1-[[3-(三氟甲基)苯基]乙酰基]-2,3-二氢-1H-吲哚-5-基]-7H-吡咯并[2,3-d]嘧啶-4-胺
• 英文名: 1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone
• 英文别名: CS-1428; QC-9698; 1-[5-(4-Amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone; Ethanone, 1-[5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-(trifluoromethyl)phenyl]-; 7-methyl-5-(1-([3-(trifluoromethyl)phenyl]acetyl)-2,3-dihydro-1H-indol-5-yI)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; S7307; GSK2606414; GSK-2606414

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 720.3±60.0 °C at 760 mmHg
• 分子式: C₂₄H₂₀F₃N₅O
• 分子量: 451.444
• 闪点: 389.4±32.9 °C
• 精确质量: 451.161987
• PSA: 77.04000
• LogP: 4.53
• 蒸汽压: 0.0±2.3 mmHg at 25°C
• 折射率: 1.668
• 储存条件: -20°C

生物活性

• 描述: GSK2606414是可渗透细胞且可口服的 PERK 抑制剂,IC50值为0.4 nM。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> PERK
  研究领域 >> 癌症
• 靶点:

  EIF2AK3 (PERK):0.4 nM (IC50)

  EIF2AK1 (HRI):420 nM (IC50)

  EIF2AK2 (PKR):696 nM (IC50)

• 体外研究: GSK2606414抑制细胞中PERK的活化[1]。
• 体内研究: GSK2606414(50和150mg/kg,po)抑制小鼠中人肿瘤异种移植物的生长[1]。
• 动物实验: 将来自细胞培养物的指数生长的BxPC3肿瘤细胞（10×10 6个细胞/小鼠）皮下植入雌性裸鼠的右胁腹。植入后16天，将具有-200mm 3肿瘤的小鼠随机分成各种治疗组（n = 8只小鼠/组）。用载体（0.5％羟丙基甲基纤维素，0.1％吐温80水溶液，pH4.8），化合物50或150mg / kg口服处理动物，投标21天。用卡尺每周测量肿瘤体积两次并计算。结果表示为给药完成时的抑制百分比，其为100 [1-（药物处理群体的平均生长）/（载体处理的对照群体的平均生长）]。使用双尾t检验进行统计分析。
• 参考文献:

  [1]. Axten JM, et al. Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulu

  [2]. Zhang M, et al. Inhibiting the Plasmodium eIF2α Kinase PK4 Prevents Artemisinin-Induced Latency. Cell Host Microbe. 2017 Dec 13;22(6):766-776.e4.

合成路线

3680-69-1 ~% 1337531-36-8

文献：Axten, Jeffrey M.; Medina, Jesus R.; Feng, Yanhong; Shu, Arthur; Romeril, Stuart P.; Grant, Seth W.; Li, William Hoi Hong; Heerding, Dirk A.; Minthorn, Elisabeth; Mencken, Thomas; Atkins, Charity; Liu, Qi; Rabindran, Sridhar; Kumar, Rakesh; Hong, Xuan; Goetz, Aaron; Stanley, Thomas; Taylor, J. David; Sigethy, Scott D.; Tomberlin, Ginger H.; Hassell, Annie M.; Kahler, Kirsten M.; Shewchuk, Lisa M.; Gampe, Robert T. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7193 - 7207

22190-33-6 ~% 1337531-36-8

文献：Axten, Jeffrey M.; Medina, Jesus R.; Feng, Yanhong; Shu, Arthur; Romeril, Stuart P.; Grant, Seth W.; Li, William Hoi Hong; Heerding, Dirk A.; Minthorn, Elisabeth; Mencken, Thomas; Atkins, Charity; Liu, Qi; Rabindran, Sridhar; Kumar, Rakesh; Hong, Xuan; Goetz, Aaron; Stanley, Thomas; Taylor, J. David; Sigethy, Scott D.; Tomberlin, Ginger H.; Hassell, Annie M.; Kahler, Kirsten M.; Shewchuk, Lisa M.; Gampe, Robert T. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7193 - 7207

837392-67-3 ~% 1337531-36-8

文献：Axten, Jeffrey M.; Medina, Jesus R.; Feng, Yanhong; Shu, Arthur; Romeril, Stuart P.; Grant, Seth W.; Li, William Hoi Hong; Heerding, Dirk A.; Minthorn, Elisabeth; Mencken, Thomas; Atkins, Charity; Liu, Qi; Rabindran, Sridhar; Kumar, Rakesh; Hong, Xuan; Goetz, Aaron; Stanley, Thomas; Taylor, J. David; Sigethy, Scott D.; Tomberlin, Ginger H.; Hassell, Annie M.; Kahler, Kirsten M.; Shewchuk, Lisa M.; Gampe, Robert T. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7193 - 7207

261732-38-1 ~% 1337531-36-8

文献：Axten, Jeffrey M.; Medina, Jesus R.; Feng, Yanhong; Shu, Arthur; Romeril, Stuart P.; Grant, Seth W.; Li, William Hoi Hong; Heerding, Dirk A.; Minthorn, Elisabeth; Mencken, Thomas; Atkins, Charity; Liu, Qi; Rabindran, Sridhar; Kumar, Rakesh; Hong, Xuan; Goetz, Aaron; Stanley, Thomas; Taylor, J. David; Sigethy, Scott D.; Tomberlin, Ginger H.; Hassell, Annie M.; Kahler, Kirsten M.; Shewchuk, Lisa M.; Gampe, Robert T. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7193 - 7207

7781-10-4 ~% 1337531-36-8

文献：Axten, Jeffrey M.; Medina, Jesus R.; Feng, Yanhong; Shu, Arthur; Romeril, Stuart P.; Grant, Seth W.; Li, William Hoi Hong; Heerding, Dirk A.; Minthorn, Elisabeth; Mencken, Thomas; Atkins, Charity; Liu, Qi; Rabindran, Sridhar; Kumar, Rakesh; Hong, Xuan; Goetz, Aaron; Stanley, Thomas; Taylor, J. David; Sigethy, Scott D.; Tomberlin, Ginger H.; Hassell, Annie M.; Kahler, Kirsten M.; Shewchuk, Lisa M.; Gampe, Robert T. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7193 - 7207

1266343-30-9 ~% 1337531-36-8

文献：Axten, Jeffrey M.; Medina, Jesus R.; Feng, Yanhong; Shu, Arthur; Romeril, Stuart P.; Grant, Seth W.; Li, William Hoi Hong; Heerding, Dirk A.; Minthorn, Elisabeth; Mencken, Thomas; Atkins, Charity; Liu, Qi; Rabindran, Sridhar; Kumar, Rakesh; Hong, Xuan; Goetz, Aaron; Stanley, Thomas; Taylor, J. David; Sigethy, Scott D.; Tomberlin, Ginger H.; Hassell, Annie M.; Kahler, Kirsten M.; Shewchuk, Lisa M.; Gampe, Robert T. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7193 - 7207

1337532-51-0 ~% 1337531-36-8

文献：Axten, Jeffrey M.; Medina, Jesus R.; Feng, Yanhong; Shu, Arthur; Romeril, Stuart P.; Grant, Seth W.; Li, William Hoi Hong; Heerding, Dirk A.; Minthorn, Elisabeth; Mencken, Thomas; Atkins, Charity; Liu, Qi; Rabindran, Sridhar; Kumar, Rakesh; Hong, Xuan; Goetz, Aaron; Stanley, Thomas; Taylor, J. David; Sigethy, Scott D.; Tomberlin, Ginger H.; Hassell, Annie M.; Kahler, Kirsten M.; Shewchuk, Lisa M.; Gampe, Robert T. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7193 - 7207

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