(2E,2'E)-1,1'-环己基亚基二[3-(3,4-二甲氧基苯基)-2-丙烯-1-酮] | 1226895-15-3

• 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 - 苯丙烷和聚酮 - 二芳基庚烷
• 中文名称: (2E,2'E)-1,1'-环己基亚基二[3-(3,4-二甲氧基苯基)-2-丙烯-1-酮]
• 英文名称: FLLL32
• 英文别名: (E)-3-(3,4-dimethoxyphenyl)-1-[1-[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]cyclohexyl]prop-2-en-1-one
• CAS: 1226895-15-3
• 化学式: C₂₈H₃₂O₆
• 分子量: 464.558
• InChiKey: NQDROBVIYYEMDQ-WFYKWJGLSA-N

物化性质

• 溶解度：
  不溶于水；乙醇中≥2.58 mg/mL； DMSO 中≥55.4 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 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

FLLL32 是一种有效的 JAK2/STAT3 抑制剂，IC50 < 5 μM。在乳腺癌细胞中，FLLL32 可以通过 IFNα 和 IL-6 来抑制 STAT3 磷酸化的诱导。

靶点

Target	Value
JAK2	<5 μM

体外研究

在 MDA-MB-231 乳腺癌和 PANC-1 胰腺癌细胞中，FLLL32 下调 STAT3 磷酸化作用及 DNA 结合活性。在 MDA-MB-231 细胞中，FLLL32 抑制菌落形成和细胞侵袭。对于人多发性骨髓瘤、恶性胶质瘤、肝癌以及结肠直肠癌，FLLL32 也会导致细胞增殖的抑制，并诱导 caspase-3 和 PARP 裂解。

体内研究

在 MDA-MB-231 异种移植的小鼠中，FLLL32 (50 mg/kg, i.p.) 显著减少肿瘤负担。在 OS-33 骨肉瘤细胞异种移植的小鼠中，通过靶向作用于 STAT3，FLLL32 (50 mg/kg, i.p.) 也能抑制肿瘤生长。

反应信息

• 作为产物：
  描述：

  1,5-二碘戊烷 、 二甲氧基姜黄素 在 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以56%的产率得到(2E,2'E)-1,1'-环己基亚基二[3-(3,4-二甲氧基苯基)-2-丙烯-1-酮]
  参考文献：
  名称：

  [EN] CURCUMIN ANALOGS AS DUAL JAK2/STAT3 INHIBITORS AND METHODS OF MAKING AND USING THE SAME
  [FR] ANALOGUES DE LA CURCUMINE EN TANT QU'INHIBITEURS DOUBLES DE JAK2/STAT3 ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION

  摘要：

  姜黄素类似物及其制备和使用方法已被披露。

  公开号：

  WO2010121007A1

文献信息

• JAK inhibitors and uses thereof
  申请人：Kim Brian

  公开号：US10973913B2

  公开（公告）日：2021-04-13

  The present invention provides methods for treating pruritus in a subject in need thereof comprising administering a therapeutically effective amount of a JAK inhibitor. Also provided are methods of intranasal administration of JAK inhibitors for use in treating pruritus.

  本发明提供了治疗有需要的受试者瘙痒症的方法，包括施用治疗有效量的 JAK 抑制剂。还提供了用于治疗瘙痒症的JAK抑制剂的鼻内给药方法。
• Curcumin Analogs as Dual JAK2/STAT3 Inhibitors and Methods of Making and Using the Same
  申请人：Li Pui-Kai

  公开号：US20120053208A1

  公开（公告）日：2012-03-01

  Curcumin analogues and methods of making and using the same are disclosed.
• PHARMACEUTICAL COMPOSITIONS FOR THE DELIVERY OF SUBSTANTIALLY WATER-INSOLUBLE DRUGS
  申请人：SINGH Mewa

  公开号：US20150080353A1

  公开（公告）日：2015-03-19

  The subject invention relates to compositions and methods useful for the in vivo delivery of substantially water-insoluble drugs, like taxol. The use of specific composition and preparation conditions enables the reproducible production of unusually water-soluble formulation, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a re-dispersible dry powder comprising nanoparticles of drug. The innovation is also based on the fact that complementary partner is also an active drug but may have a different mode action with respect to primary molecule of the hybrid drug. The complementary molecule has multiple properties like antioxidant, antimicrobial, anti-inflammatory, anti-allergic, cox-2 inhibitors, etc. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable.
• JAK INHIBITORS AND USES THEREOF
  申请人：Kim Brian

  公开号：US20200282051A1

  公开（公告）日：2020-09-10

  The present invention provides methods for treating pruritus in a subject in need thereof comprising administering a therapeutically effective amount of a JAK inhibitor. Also provided are methods of intranasal administration of JAK inhibitors for use in treating pruritus.
• ANTI-CANCER TREATMENT OF PRESELECTED SUBJECTS AND SCREENING METHODS TO IDENTIFY SUSCEPTIBLE SUBJECTS
  申请人：TUDAG TU Dresden Aktiengesellschaft

  公开号：US20210231661A1

  公开（公告）日：2021-07-29

  The invention provides methods of screening a subject for a proliferative disease risk factor which comprises detecting the presence or absence of target cells. The presence of target cells in the subject indicates the subject is at increased risk of developing a proliferative disease or recurrence of a previously treated proliferative disease and defines a new patient subgroup susceptible for treatment with selected anti-proliferative compounds. Methods of screening compounds for the treatment of proliferative diseases based on the presence of target cells and the expression of certain biomarkers by said target cells are also disclosed, along with appropriate compounds and their use in methods of treating such diseases.