IWP2;N-(6-甲基-2-苯并噻唑基)-2-[(3,4,6,7-四氢-4-氧代-3-苯基噻吩并[3,2d]嘧啶-2-基)硫基]乙酰胺 | 686770-61-6

• 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 - 噻吩并嘧啶酮衍生物
• 中文名称: IWP2;N-(6-甲基-2-苯并噻唑基)-2-[(3,4,6,7-四氢-4-氧代-3-苯基噻吩并[3,2d]嘧啶-2-基)硫基]乙酰胺
• 英文名称: N-(6-Methyl-2-benzothiazolyl)-2-[(3,4,6,7-tetrahydro-4-oxo-3-phenylthieno[3,2-d]pyrimidin-2-yl)thio]-acetamide
• 英文别名: N-(6-methyl-1,3-benzothiazol-2-yl)-2-[(4-oxo-3-phenyl-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]acetamide
• CAS: 686770-61-6
• 化学式: C₂₂H₁₈N₄O₂S₃
• 分子量: 466.6
• InChiKey: WRKPZSMRWPJJDH-UHFFFAOYSA-N

物化性质

• 熔点：
  257 °C(dec.)
• 密度：
  1.52±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  154
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• WGK Germany：
  2
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

制备方法与用途

生物活性

IWP-2是一种Wnt信号和分泌抑制剂，在无细胞试验中IC50为27 nM。它选择性地阻断Porcn介导的Wnt棕榈酰化，通常不会干扰Wnt/β-catenin通路，并且不对Wnt刺激的细胞反应产生影响。IWP-2还特定低抑制CK1δ。

体外研究

在再生医学和抗癌领域，IWP-2表现出极高的有效性。它通过失活Porcn来发挥作用，Porcn是一种与O-酰基转移酶(MBOAT)结合的膜蛋白，并且选择性地抑制Wnt棕榈酰化。IWP-2能够抑制Lrp6受体和Dvl2在Wnt依赖条件下的磷酸化，同时减少β-catenin的积累。

特征

IWP-2是Porcn介导的Wnt分泌的选择性抑制剂。

靶点

目标	值
Wnt (无细胞试验)	27 nM
	40 nM

文献信息

• PRODUCTION METHOD FOR NERVE TISSUE
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：EP3211072A1

  公开（公告）日：2017-08-30

  The present invention provides a method for producing neural cells or a neural tissue, including the following steps (1) - (3): (1) a first step of culturing pluripotent stem cells in the absence of feeder cells and in a medium containing 1) a TGFβ family signal transduction pathway inhibiting substance and/or a Sonic hedgehog signal transduction pathway activating substance, and 2) a factor for maintaining undifferentiated state, (2) a second step of culturing the cells obtained in the first step in suspension to form a cell aggregate, and (3) a third step of culturing the aggregate obtained in the second step in suspension in the presence or absence of a differentiation-inducing factor to obtain an aggregate containing neural cells or a neural tissue.

  本发明提供了一种生产神经细胞或神经组织的方法，包括以下步骤（1）-（3）： (1) 第一步：在没有饲养细胞的情况下，在含有以下物质的培养基中培养多能干细胞：1）TGFβ 家族信号转导通路抑制物质和/或 Sonic hedgehog 信号转导通路激活物质；2）维持未分化状态的因子、 (2) 第二步，将第一步中获得的细胞悬浮培养以形成细胞聚集体，以及 (3) 第三步：在分化诱导因子存在或不存在的情况下，悬浮培养第二步得到的聚集体，以得到含有神经细胞或神经组织的聚集体。
• METHOD FOR PRODUCING RETINAL PIGMENT EPITHELIAL CELLS
  申请人：Sumitomo Dainippon Pharma Co., Ltd.

  公开号：EP3354721A1

  公开（公告）日：2018-08-01

  The present invention provides a method for more efficiently producing retinal pigment epithelial cells from pluripotent stem cells. The method of the present invention for producing retinal pigment epithelial cells includes the following steps: (1) a first step for culturing a pluripotent stem cell in a medium comprising an FGF receptor inhibitor and/or an MEK inhibitor for a period of not more than 30 days, and (2) a second step for culturing the cell obtained in the first step in the presence of a Nodal signal transduction pathway inhibitor and/or a Wnt signal transduction pathway inhibitor to form a retinal pigment epithelial cell.

  本发明提供了一种更有效地利用多能干细胞生产视网膜色素上皮细胞的方法。 本发明生产视网膜色素上皮细胞的方法包括以下步骤：(1)第一步，在含有FGF受体抑制剂和/或MEK抑制剂的培养基中培养多能干细胞，时间不超过30天；(2)第二步，在Nodal信号转导通路抑制剂和/或Wnt信号转导通路抑制剂存在下培养第一步中获得的细胞，以形成视网膜色素上皮细胞。
• CELL AGGREGATE INCLUDING RETINAL TISSUE AND PRODUCTION METHOD THEREFOR
  申请人：Riken

  公开号：EP3680326A1

  公开（公告）日：2020-07-15

  A sphere-like cell aggregate according to one embodiment of the present invention comprises: a core part containing neural retina; and a covering part continuously or discontinuously covering at least a portion of a surface of the core part, wherein (1) in the neural retina, a neural retinal layer including at least a photoreceptor layer is formed, wherein the photoreceptor layer contains one or more types of cells selected from the group consisting of at least a photoreceptor cell, a photoreceptor progenitor cell, and a retinal progenitor cell, and the cells contained in the photoreceptor layer are continuously present in a tangential direction to the surface of the core part; (2) the covering part contains retinal pigment epithelial cells in contact with each other; (3) the sphere-like cell aggregate is free of a crystalline lens, a vitreous, a cornea, and a blood vessel; and (4) the retinal pigment epithelial cells do not constitute an epithelial structure continued with the neural retinal layer.

  根据本发明一个实施例的球状细胞聚集体包括：包含神经视网膜的核心部分；以及连续或不连续地覆盖核心部分至少一部分表面的覆盖部分，其中 (1) 在神经视网膜中，形成至少包括感光层的神经视网膜层，其中感光层包含选自至少感光细胞、感光祖细胞和视网膜祖细胞所组成的组中的一种或多种细胞，感光层中包含的细胞在核心部分表面的切线方向上连续存在； (2) 覆盖部分包含相互接触的视网膜色素上皮细胞； (3) 球状细胞集合体不含晶状体、玻璃体、角膜和血管；以及 (4) 视网膜色素上皮细胞不构成与神经视网膜层相连的上皮结构。
• METHOD FOR MATURATION OF RETINAL TISSUE CONTAINING CONTINUOUS EPITHELIUM
  申请人：RIKEN

  公开号：EP3656852A1

  公开（公告）日：2020-05-27

  The present invention provides a method for maintaining a continuous epithelial structure of a retinal tissue including culturing the retinal tissue in a medium comprising a methyl group donor or a substrate of the methyl group donor at a concentration at which cell differentiation of a neural retinal progenitor cell is suppressed, and a neurite extension inhibitor at a concentration at which neurite extension is suppressed.

  本发明提供了一种维持视网膜组织连续上皮结构的方法，包括在一种培养基中培养视网膜组织，该培养基包括甲基基团供体或甲基基团供体的底物（浓度为抑制神经视网膜祖细胞的细胞分化）和神经元延伸抑制剂（浓度为抑制神经元延伸）。
• METHOD FOR AMPLIFYING CONE PHOTORECEPTORS OR ROD PHOTORECEPTORS USING DORSALIZATION SIGNAL TRANSMITTER OR VENTRALIZATION SIGNAL TRANSMITTER
  申请人：RIKEN

  公开号：EP3683304A1

  公开（公告）日：2020-07-22

  The present invention aims to provide a retinal tissue rich in cone photoreceptor precursors and/or cone photoreceptors, a retinal tissue rich in rod photoreceptor precursors and/or rod photoreceptors, and a production method thereof and the like. i) A method for increasing a proportion of a cone photoreceptor precursor and a cone photoreceptor in a photoreceptor precursor and a photoreceptor contained in a retinal tissue, including a step of culturing a retinal tissue, in an initial developmental stage to a stage where an emergence rate of a cone photoreceptor precursor reaches maximum, in a medium containing a dorsalization signal transmitter at a concentration sufficient to suppress expression of a ventral marker, or ii) a method for increasing a proportion of a rod photoreceptor precursor and a rod photoreceptor in a photoreceptor precursor and a photoreceptor contained in a retinal tissue, including a step of culturing a retinal tissue, in an initial developmental stage to a stage where an emergence rate of a cone photoreceptor precursor reaches maximum, in a medium containing a ventralization signal transmitter at a concentration sufficient to promote expression of a ventral marker.

  本发明旨在提供一种富含视锥光感受器前体和/或视锥光感受器的视网膜组织、一种富含杆状光感受器前体和/或杆状光感受器的视网膜组织及其生产方法等。i) 一种增加视网膜组织中所含感光前体和感光体中锥体感光前体和锥体感光体比例的方法，包括以下步骤：在初始发育阶段到锥体感光前体出现率达到最大值的阶段，在含有背化信号传递体的培养基中培养视网膜组织，培养基的浓度足以抑制腹侧标记物的表达、或 ii）一种提高视网膜组织中包含的感光前体和感光体中杆感光前体和杆感光体比例的方法，包括以下步骤：在含有腹侧化信号转导物的培养基中，以足以促进腹侧标记表达的浓度，将视网膜组织从初始发育阶段培养到锥感光前体出现率达到最大值的阶段。