Naquotinib

• 常用名: Naquotinib
• 英文名: Naquotinib
• CAS号: 1448232-80-1
• 分子量: 562.706
• 密度: 1.2±0.1 g/cm3
• 沸点: 717.6±60.0 °C at 760 mmHg
• 分子式: C₃₀H₄₂N₈O₃
• 熔点: N/A
• 闪点: 387.8±32.9 °C

Naquotinib用途

Naquotinib (ASP8273) 是有口服活性，不可逆的 EGFR 突变体抑制剂；对EGFR突变体和EGFR的 IC₅₀ 值分别为8-33和230 nM。

Naquotinib名称

• 中文名: 6-乙基-3-[[4-[4-(4-甲基-1-哌嗪基)-1-哌啶基]苯基]氨基]-5-[[(3R)-1-(1-氧代-2-丙烯-1-基)-3-吡咯烷基]氧基]-2-吡嗪甲酰胺
• 英文名: 6-Ethyl-3-[[4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[[(3R)-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]oxy]-2-pyrazinecarboxamide

Naquotinib生物活性

• 描述: Naquotinib (ASP8273) 是有口服活性,不可逆的 EGFR 突变体抑制剂；对EGFR突变体和EGFR的 IC50 值分别为8-33和230 nM。
• 相关类别:
  研究领域 >> 癌症
• 靶点:

  EGFR:230 nM (IC50)

  EGFRT790M

  EGFRL858R/T790M

  EGFRL858R

  EGFRExon 19 deletion/T790M

• 体外研究: 在使用内源性EGFR依赖性细胞的测定中,Naquotinib抑制PC-9(del ex19),HCC827(del ex19),NCI-H1975(del ex19/T790M)和PC-9ER(del ex19/T790M)的生长,IC50为8-33 nM [1]。 Naquotinib在HCC827和NCI-H1975中选择性抑制EGFR及其下游信号通路ERn和Akt的磷酸化,而仅在1000nM时检测到抑制作用。在NCI-H1650(del ex19)中,Naquotinib抑制细胞生长。 IC50值为70nM,而其他EGFR-TKI仅部分有效[2]。
• 体内研究: 口服Naquotinib治疗剂量依赖性地诱导NCI-H1975(L858R/T790M),HCC827(del ex19)和PC-9(del ex19)异种移植模型中的肿瘤消退。给药方案不影响Naquotinib的疗效。在NCI-H1975异种移植模型中,在Naquotinib处理14天后实现肿瘤的完全消退。停止Naquotinib治疗后超过85天,50％的小鼠完全消退[2]。
• 参考文献:

  [1]. Sakagami H, et al. ASP8273, a novel mutant-selective irreversible EGFR inhibitor, inhibits growth of non-small cell lung cancer (NSCLC) cells with EGFR activating and T790M resistance mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1728. doi:10.1158/1538-7445.AM2014-1728

  [2]. Konagai S, et al. ASP8273 selectively inhibits mutant EGFR signal pathway and induces tumor shrinkage in EGFR mutated tumor models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2586. doi:10.1158/1538-7445.AM2015-2586

Naquotinib物理化学性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 717.6±60.0 °C at 760 mmHg
• 分子式: C₃₀H₄₂N₈O₃
• 分子量: 562.706
• 闪点: 387.8±32.9 °C
• 精确质量: 562.338013
• LogP: 3.74
• 外观性状: 粉末
• 蒸汽压: 0.0±2.3 mmHg at 25°C
• 折射率: 1.624
• 储存条件: -20℃

Naquotinib英文别名

• Naquotinib
• 6-Ethyl-3-{4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}-5-{[(3R)-1-(prop-2-enoyl)pyrrolidin-3-yl]oxy}pyrazine-2-carboxamide
• UNII-47DD4548PB
• 2-Pyrazinecarboxamide, 6-ethyl-3-[[4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[[(3R)-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]oxy]-
• ASP8273
• 5-{[(3R)-1-Acryloyl-3-pyrrolidinyl]oxy}-6-ethyl-3-({4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl}amino)-2-pyrazinecarboxamide
• 6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-{[(3R)-1-(1-oxoprop-2-en-1-yl)pyrrolidin-3-yl]oxy}pyrazine-2-carboxamide