IWR-1 | 1127442-82-3

• 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 - 苯类化合物 - 苯和取代衍生物
• 英文名称: IWR-1
• 英文别名: IWR-1-endo；4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-quinolin-8-ylbenzamide
• CAS: 1127442-82-3
• 化学式: C₂₅H₁₉N₃O₃
• 分子量: 409.444
• InChiKey: ZGSXEXBYLJIOGF-ALFLXDJESA-N

物化性质

• 比旋光度：
  -3.0～+3.0°(20℃/D)(c=0.1,CH3CN)
• 沸点：
  643.9±55.0 °C(Predicted)
• 密度：
  1.425±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶，5mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  79.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 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

IWR-1-endo (endo-IWR 1)是一种Wnt通路抑制剂，在表达 Wnt3A 的 L-细胞中IC50为180 nM，诱导Axin2蛋白水平，并通过稳定Axin骨架破坏复合体来促进β-catenin磷酸化。

靶点

Target	Value
Wnt (L-cells expressing Wnt3A)	180 nM

体外研究

IWR-1 和XAV939作为Wnt通路的可逆抑制剂，在体内外具有相似的药理作用，IWR-1通过与Axin相互作用而发挥效果,而XAV939直接与TNKS结合。

反应信息

• 作为反应物：
  描述：

  IWR-1 在 macroporous borohydride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以36.7%的产率得到(+/-)-4-((3aS,4R,7-S,7aR)-1-hydroxy-3-oxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)-N-(quinolin-8-yl)benzamide
  参考文献：
  名称：

  Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors

  摘要：

  Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates beta-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of beta-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).

  DOI：

  10.1021/jm4000038

文献信息

• [EN] NOVEL PREPARATION METHOD OF QUINOLINE N-OXIDE DERIVATIVE WITH AMIDE GROUP<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION D'UN DÉRIVÉ DE N-OXYDE DE QUINOLÉINE AYANT UN GROUPE AMIDE
  申请人：INST BASIC SCIENCE

  公开号：WO2015160125A1

  公开（公告）日：2015-10-22

  Provided are a preparation method of a quinoline N-oxide derivative with an amide group capable of easily introducing the amide group into the quinoline N-oxide derivative by simplified processes and mild reaction conditions, and a quinoline N-oxide derivative with an amide group prepared by using the same.

  提供了一种奎诺啉N-氧化物衍生物的制备方法，该方法能够通过简化的过程和温和的反应条件将酰胺基团轻松引入奎诺啉N-氧化物衍生物中，并且提供了使用该方法制备的带有酰胺基团的奎诺啉N-氧化物衍生物。
• 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。
• 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。