N-(5-苯基-2-吡啶基)-2-[(3,4,6,7-四氢-4-氧代-3-苯基噻吩并[3,2-d]嘧啶-2-基)硫基]乙酰胺 | 1427782-89-5

• 物质功能分类: 生物化工 - 抑制剂 - 干细胞及Wnt信号通路(Stem Cells & Wnt)
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: N-(5-苯基-2-吡啶基)-2-[(3,4,6,7-四氢-4-氧代-3-苯基噻吩并[3,2-d]嘧啶-2-基)硫基]乙酰胺
• 中文别名: IWP-L6抑制剂；N-(5-苯基-2-吡啶基)-2-[(3,4,6,7-四氢-4-氧代-3-苯基噻吩并[3,2-d]嘧啶-2-基)硫代]乙酰胺；PORCN抑制剂(IWPL6)；N-(5-苯基-2-吡啶基)-2-[(3,4,6,7-四氢-4-氧代-3-苯基噻吩并[3,2-D]嘧啶-2-基)硫基]乙酰胺
• 英文名称: IWP-L6
• 英文别名: 2-((4-Oxo-3-phenyl-3,4,6,7-tetrahydrothieno[3,2-d]pyrimidin-2-yl)thio)-N-(5-phenylpyridin-2-yl)acetamide；2-[(4-oxo-3-phenyl-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(5-phenylpyridin-2-yl)acetamide
• CAS: 1427782-89-5
• 化学式: C₂₅H₂₀N₄O₂S₂
• 分子量: 472.591
• InChiKey: QESQGTFWEQMCMH-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO 中≥22.45 mg/mL；不溶于水；不溶于乙醇

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H320,H335

制备方法与用途

生物活性

IWP-L6 (Porcn Inhibitor III) 是高效强效的Porcn抑制剂，EC50值为0.5 nM。

体外研究

IWP-L6能够阻断HEK293细胞中细胞质Wnt通路效应器Dvl2的磷酸化作用。此外，在培养的胚肾中，IWP-L6通过可逆地阻断Wnt信号而抑制由Wnt介导的分支形态发生。

体内研究

IWP-L6在人血浆中能够稳定超过24小时，在大鼠血浆中的半衰期为190分钟（t1/2 = 190 分钟），在小鼠血浆中的半衰期仅为2分钟（t1/2 = 2 分钟），并且在小鼠肝脏S9组分中迅速代谢。在斑马鱼胚胎中，IWP-L6有效抑制后侧枢椎的形成，这一过程依赖于Wnt/β-连环蛋白信号通路。

反应信息

• 作为产物：
  描述：

  甲基3-氨基-4,5-二氢-2-噻吩羧酸酯 在 吡啶 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-(5-苯基-2-吡啶基)-2-[(3,4,6,7-四氢-4-氧代-3-苯基噻吩并[3,2-d]嘧啶-2-基)硫基]乙酰胺
  参考文献：
  名称：

  [EN] HIGHLY POTENT INHIBITORS OF PORCUPINE
  [FR] INHIBITEURS TRÈS PUISSANTS DE PORC-ÉPIC

  摘要：

  公开号：

  WO2014186450A3

文献信息

• HIGHLY POTENT INHIBITORS OF PORCUPINE
  申请人：The Board of Regents of the University of Texas System

  公开号：US20160115177A1

  公开（公告）日：2016-04-28

  The present invention generally relates to protein signalling. In particular, compounds that inhibit the Wnt protein signalling pathway are disclosed. Such compounds may be used in the treatment of Wnt protein signalling-related diseases and conditions such as cancer, degenerative diseases, type II diabetes and osteopetrosis.

  本发明一般涉及蛋白质信号传递。具体而言，本发明揭示了抑制Wnt蛋白质信号通路的化合物。这样的化合物可以用于治疗与Wnt蛋白质信号通路相关的疾病和病况，如癌症、退行性疾病、二型糖尿病和骨质硬化。
• CELL AGGREGATION INCLUDING OLFACTORY NEURON OR PRECURSOR CELL THEREOF, AND METHOD FOR PRODUCING SAME
  申请人：SUMITOMO CHEMICAL COMPANY LIMITED

  公开号：EP3842527A1

  公开（公告）日：2021-06-30

  A method for producing a cell cluster including an olfactory receptor neuron or a precursor cell thereof, comprising the following steps (1) to (3): step (1) of suspension-culturing a pluripotent stem cell in the presence of a Wnt signaling pathway inhibitory substance to form a cell aggregate; step (2) of suspension-culturing the cell aggregate obtained in the step (1) in the presence of a BMP signaling pathway-activating substance; and step (3) of suspension-culturing the cell aggregate obtained in the step (2) to obtain the cell cluster, wherein step (3) comprises at least one step selected from the group consisting of: step (3a) of suspension-culturing in the presence of an FGF signaling pathway-activating substance; step (3b) of suspension-culturing in the presence of a BMP signaling pathway inhibitory substance; and step (3c) of culturing in the presence of an FGF signaling pathway-activating substance and a BMP signaling pathway inhibitory substance.

  一种生产包括嗅觉受体神经元或其前体细胞的细胞团的方法，包括以下步骤(1)至(3)：步骤(1)在Wnt信号通路抑制物质存在下悬浮培养多能干细胞以形成细胞聚集体；步骤(2)在BMP信号通路激活物质存在下悬浮培养步骤(1)中获得的细胞聚集体；以及步骤(3)悬浮培养步骤(2)中获得的细胞聚集体以获得细胞簇，其中步骤(3)包括至少一个选自由以下组成的组的步骤：在 FGF 信号通路激活物质存在下进行悬浮培养的步骤(3a)； 在 BMP 信号通路抑制物质存在下进行悬浮培养的步骤(3b)；以及 在 FGF 信号通路激活物质和 BMP 信号通路抑制物质存在下进行培养的步骤(3c)。
• In vitro method of differentiating a human pluripotent stem cell population into a cardiomyocyte cell population
  申请人：Ncardia B.V.

  公开号：US11136551B2

  公开（公告）日：2021-10-05

  The current invention relates to a method of differentiation of human pluripotent stem cells into a human stem-cell derived population of cardiomyocytes. The method comprises the use of specific combination of steps and compounds to induce and/or promote differentiation. The method also comprises steps directed to further maturation of the cardiomyocytes obtained with the method of the invention. Also provided are kits for use in a method of differentiation as well as cell populations obtainable with the method disclosed.

  本发明涉及一种将人类多能干细胞分化为人类干细胞衍生的心肌细胞群体的方法。该方法包括使用特定的步骤和化合物组合来诱导和/或促进分化。该方法还包括进一步成熟用本发明方法获得的心肌细胞的步骤。本发明还提供了用于分化方法的试剂盒以及可通过本发明方法获得的细胞群。
• The Development of Highly Potent Inhibitors for Porcupine
  作者：Xiaolei Wang、Jesung Moon、Michael E. Dodge、Xinchao Pan、Lishu Zhang、Jordan M. Hanson、Rubina Tuladhar、Zhiqiang Ma、Heping Shi、Noelle S. Williams、James F. Amatruda、Thomas J. Carroll、Lawrence Lum、Chuo Chen

  DOI：10.1021/jm400159c

  日期：2013.3.28

  Porcupine is a member of the membrane-bound O-acyltransferase family of proteins. It catalyzes the palmitoylation of Wnt proteins, a process required for their secretion and activity. We recently disclosed a class of small molecules (IWPs) as the first reported Porcn inhibitors. We now describe the structure-activity relationship studies and the identification of subnanomolar inhibitors. We also report herein the effects of IWPs on Wnt-dependent developmental processes, including zebrafish posterior axis formation and kidney tubule formation.
• AN IN VITRO METHOD OF DIFFERENTIATING A HUMAN PLURIPOTENT STEM CELL POPULATION INTO A CARDIOMYOCYTE CELL POPULATION
  申请人：Pluriomics B.v.

  公开号：EP3344758A1

  公开（公告）日：2018-07-11