N-(4-异丙基-2-(3-氧代-3,4-二氢喹喔啉-2-基)苯基)噻吩-2-甲酰胺 | 1404437-62-2

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(4-异丙基-2-(3-氧代-3,4-二氢喹喔啉-2-基)苯基)噻吩-2-甲酰胺
• 中文别名: N-[2-(3,4-二氢-3-氧代-2-喹喔啉基)-4-(1-甲基乙基)苯基]-2-噻吩甲酰胺；N-[2-(3,4-二氢-3-氧代-2-喹喔啉基)-4-(1-甲基乙基)苯基]-2-噻吩羧酰胺
• 英文名称: N-(4-isopropyl-2-(3-oxo-3,4-dihydroquinoxalin-2-yl)phenyl)thiophene-2-carboxamide
• 英文别名: N-[2-(3,4-Dihydro-3-oxo-2-quinoxalinyl)-4-(1-methylethyl)phenyl]-2-thiophenecarboxamide；N-[2-(3-oxo-4H-quinoxalin-2-yl)-4-propan-2-ylphenyl]thiophene-2-carboxamide
• CAS: 1404437-62-2
• 化学式: C₂₂H₁₉N₃O₂S
• 分子量: 389.478
• InChiKey: HWOYIOLMBQSTQS-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：33mg/mL； DMF:PBS (pH 7.2) (1:4)：0.2 mg/mL；二甲基亚砜：20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

生物活性

ML281 是一种有效的 STK33（Serine/threonine kinase 33）选择性抑制剂，IC50值为0.014 μM。ML281 对KRAS依赖性癌细胞系具有选择性的细胞毒性。

靶点

Target	Value
STK33 (Cell-free assay)	0.014 μM

体外研究

ML281（浓度：10 μM；时间：72小时）抑制了NCI-H446细胞的活力。

实验细节

• 细胞系：NCI-H446细胞
• 浓度：10 μM
• 培养时间：72小时
• 结果：抑制了NCI-H446细胞的活力

反应信息

• 作为产物：
  描述：

  2-噻吩甲酰氯 、 5-异丙基靛红 在 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 15.5h， 生成 N-(4-异丙基-2-(3-氧代-3,4-二氢喹喔啉-2-基)苯基)噻吩-2-甲酰胺
  参考文献：
  名称：

  A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells

  摘要：

  The KRAS oncogene is found in up to 30% of all human tumors. In 2009, RNAi experiments revealed that lowering mRNA levels of a transcript encoding the serine/threonine kinase STK33 was selectively toxic to KRAS-dependent cancer cell lines, suggesting that small-molecule inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Molecular Libraries Small Molecule Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chemical probe ML281 that showed low nanomolar inhibition of purified recombinant STK33 and a distinct selectivity profile as compared to other STK33 inhibitors that were reported in the course of these studies. Even at the highest concentration tested (10 mu M), ML281 had no effect on the viability of KRAS-dependent cancer cells. These results are consistent with other recent reports using small-molecule STK33 inhibitors. Small molecules having different chemical structures and kinase-selectivity profiles are needed to fully understand the role of STK33 in KRAS-dependent cancers. In this regard, ML281 is a valuable addition to small-molecule probes of STK33.

  DOI：

  10.1021/ml300246r