1,4,5,6,7,8-六氢-2,7,7-三甲基-4-(4-硝基苯基)-5-氧代-3-喹啉羧酸环己基酯 | 313967-18-9

• 物质功能分类: 生物化工 - 抑制剂 - 蛋白酶体(Proteases)
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 1,4,5,6,7,8-六氢-2,7,7-三甲基-4-(4-硝基苯基)-5-氧代-3-喹啉羧酸环己基酯
• 英文名称: FLI-06
• 英文别名: Cyclohexyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate；cyclohexyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,6,8-tetrahydroquinoline-3-carboxylate
• CAS: 313967-18-9
• 化学式: C₂₅H₃₀N₂O₅
• 分子量: 438.524
• InChiKey: SWWVFYHSSOWZMF-UHFFFAOYSA-N

物化性质

• 熔点：
  199-202oC
• 沸点：
  597.5±50.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶5mg/mL，澄清（加热）

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• WGK Germany：
  3
• 海关编码：
  29339900
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

FLI-06 是一种靶向Notch信号通路的新型抑制剂，EC50是2.3 μM。

靶点

Target	Value
Notch (Cell-based assay)	2.3 μM(EC50)

体外研究

在过表达Notch绿色荧光蛋白的Hela细胞中，FLI-06 抑制Notch的转运和处理。FLI-06改变APP的成熟模式，终止APPs的释放。 在肾上皮细胞系293细胞中，稳定转染突变型的APP导致大量的淀粉样沉淀。FLI-06 破坏高尔基复合体，在内质网从管状到片状的形态转换过程中，抑制内质网转运前总蛋白的分泌。

体内研究

在斑马鱼胚胎中，50uM的FLI-06抑制内源性的Notch信号。

反应信息

• 作为反应物：
  描述：

  1,4,5,6,7,8-六氢-2,7,7-三甲基-4-(4-硝基苯基)-5-氧代-3-喹啉羧酸环己基酯 在 manganese(IV) oxide 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到cyclohexyl 2,7,7-trimethyl-4-(4'-nitrophenyl)-5-oxo-5,6,7,8-tetrahydroquinoline-3-carboxylate
  参考文献：
  名称：

  [EN] INHIBITORS OF THE NOTCH SIGNALLING PATHWAY AND SECRETION FOR USE IN MEDICINE
  [FR] INHIBITEURS DE LA VOIE DE SIGNALISATION NOTCH ET DE SÉCRÉTION POUR USAGE MÉDICAL

  摘要：

  该发明涉及二氢吡啶化合物作为抑制Notch信号通路和/或抑制分泌以治疗分泌依赖性疾病，例如癌症或衰老相关的衰老，以及其制药组合物和治疗方法。

  公开号：

  WO2013178821A1

文献信息

• Derivation of hepatic stem cells and mature liver cell types and uses thereof
  申请人：AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

  公开号：US10683484B2

  公开（公告）日：2020-06-16

  This application describes liver stem cells (LSC), and differentiated hepatocytes, cholangiocytes, and 3D cellular structures derived therefrom. Methods for producing LSC and mature, differentiated hepatocytes and cholangiocytes in culture are provided. Also provided are cell culture systems and cell culture media for producing a homogenous population of liver stem cells that remain in an undifferentiated state over multiple passages in culture. The LSC and methods are useful for producing homogenous populations of hepatocytes and cholangiocytes for downstream applications. The LSC can be transplanted into subjects to treat liver diseases.

  本申请介绍了肝干细胞（LSC）、分化的肝细胞、胆管细胞以及由此衍生的三维细胞结构。本申请提供了在培养过程中产生 LSC 以及成熟、分化的肝细胞和胆管细胞的方法。此外，还提供了细胞培养系统和细胞培养基，用于产生在培养过程中多次传代保持未分化状态的同源肝干细胞群。这种肝干细胞和方法可用于生产下游应用所需的同源肝细胞和胆管细胞。肝干细胞可移植到受试者体内治疗肝脏疾病。
• INHIBITORS OF THE NOTCH SIGNALLING PATHWAY AND SECRETION FOR USE IN MEDICINE
  申请人：Leibniz-Institut für Altersforschung - Fritz-Lipmann-Institut e.V.

  公开号：EP2854809A1

  公开（公告）日：2015-04-08
• DERIVATION OF HEPATIC STEM CELLS AND MATURE LIVER CELL TYPES AND USES THEREOF
  申请人：Agency for Science, Technology and Research

  公开号：EP3307874A1

  公开（公告）日：2018-04-18
• COMBINATIONS OF LSD1 INHIBITORS FOR USE IN THE TREATMENT OF SOLID TUMORS
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20170281567A1

  公开（公告）日：2017-10-05

  The instant invention relates to therapeutic combinations of LSD1 inhibitors and one or more other active pharmaceutical ingredient(s) or pharmaceutically acceptable salts thereof. The combinations are particularly useful for treating neoplastic diseases, such as cancer, particularly small cell lung cancer (SCLC).
• METHODS FOR PRODUCING LYMPHOCYTE PROGENITORS
  申请人：MURDOCH CHILDRENS RESEARCH INSTITUTE

  公开号：US20200399390A1

  公开（公告）日：2020-12-24

  The invention relates to a method for producing a lymphocyte progenitor, the method comprising culturing a pluripotent stem cell (PSC)-derived CD34+ cell at an air-liquid interface (ALI). The invention also relates to a method for producing a B-cell progenitor, the method comprising co-culturing a PSC-derived CD34+ cell and a stromal cell in a medium comprising a CD117 activator and a NOTCH1 inhibitor. The invention further relates to a T-cell progenitor and a B-cell progenitor when produced by the methods of the invention and to use of the T-cell progenitor in the manufacture of T cell with defined antigen specificity, optionally a chimeric antigen receptor (CAR) T cell, and use of the B-cell progenitor in the manufacture of an antibody.