4-甲基-5-[[（（2S）-2-甲基-1,4-二氮杂潘-1-基]磺酰基]异喹啉二盐酸盐 | 871543-07-6

• 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 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 4-甲基-5-[[（（2S）-2-甲基-1,4-二氮杂潘-1-基]磺酰基]异喹啉二盐酸盐
• 中文别名: RHO激酶抑制剂(H-1152DIHYDROCHLORIDE)；H-1152双盐酸盐；H-1152二氢氯化物；H1152二盐酸盐；871543-7-6
• 英文名称: H-1152 Dihydrochloride
• 英文别名: 4-methyl-5-[[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinoline;dihydrochloride
• CAS: 871543-07-6；451462-58-1
• 化学式: C16H23Cl2N3O2S
• 分子量: 392.3
• InChiKey: BFOPDSJOLUQULZ-GXKRWWSZSA-N

物化性质

• 熔点：
  182-184°C
• 溶解度：
  溶于甲醇、水

计算性质

• 辛醇/水分配系数(LogP)：
  2.76
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  70.7
• 氢给体数：
  3
• 氢受体数：
  5

制备方法与用途

生物活性

H-1152 dihydrochloride 是一种膜通透的，选择性的 ROCK 抑制剂，Ki 值为 1.6 nM，对 ROCK2 的 IC50 值为 12 nM。

靶点

ROCKII 12 nM (IC 50 )

CaMKII 0.18 μM (IC 50 )

PKG 0.36 μM (IC 50 )

AuroraA 0.745 μM (IC 50 )

PKA 3.03 μM (IC 50 )

Src 3.06 μM (IC 50 )

PKC 5.68 μM (IC 50 )

Abl 7.77 μM (IC 50 )

MKK4 16.9 μM (IC 50 )

MLCK 28.3 μM (IC 50 )

EGFR 50 μM (IC 50 )

GSK3α 60.7 μM (IC 50 )

AMPK 100 μM (IC 50 )

P38α 100 μM (IC 50 )

体外研究

H-1152 dihydrochloride is an inhibitor of Rho-kinase, with an IC ₅₀ of 12 nM for ROCK2. H-1152 (H-1152P) also shows less inhibitory activities against CaMKII, PKG, AuroraA, PKA, Src, PKC, MLCK, Abl, EGFR, MKK4, GSK3α, AMPK, and P38α, with IC ₅₀ s of 0.180, 0.360, 0.745, 3.03, 3.06, 5.68, 28.3, 7.77, 50.0, 16.9, 60.7, 100, and 100 μM, respectively. H-1152 potently inhibits Rho kinase, with a K _i of 1.6 nM, and slightly suppresses PKA, PKC and MLCK, with K _i s of 0.63, 9.27, and 10.1 μM, respectively. H-1152 (0.1-10 µM) highly inhibits MARCKS phosphorylation, with an IC ₅₀ value of 2.5 µM in LPA-treated cells, but shows no such obvious effects in PDBu-treated cells. H-1152 (0.5-10 μM) cuases no decreased neuronal survival. H-1152 (1, 5 or 10 μM) also exerts no alterations in the ratios of different neuronal morphologies. Furthermore, H-1152 (10 μM) increases neurite length in both BMP4 and LIF cultures.

文献信息

• CULTURE MEDIUM FOR EPITHELIAL STEM CELLS AND ORGANOIDS COMPRISING SAID STEM CELLS
  申请人：Koninklijke Nederlandse Akademie van Wetenschappen

  公开号：EP3061808A2

  公开（公告）日：2016-08-31

  The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising said epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of said culture medium, and to crypt-villus organoids, gastric organoids and pancreatic organoids that are formed in said culture medium.

  本发明涉及一种培养上皮干细胞、包括所述上皮干细胞或腺瘤细胞的分离组织片段的方法，以及在培养上皮干细胞和分离组织片段时，在骨形态发生蛋白（BMP）抑制剂、有丝分裂生长因子和Wnt激动剂存在下培养细胞或片段的方法。本发明还涉及一种包含 BMP 抑制剂、有丝分裂生长因子和 Wnt 激动剂的细胞培养基，涉及所述培养基的使用，以及在所述培养基中形成的隐窝-绒毛器官组织、胃器官组织和胰腺器官组织。
• CELL CULTURE MEDIUM, CULTURE METHOD, AND ORGANOID
  申请人：Keio University

  公开号：EP3418376A1

  公开（公告）日：2018-12-26

  The present invention provides a cell culture medium with which serum-free long-term culture of an epithelial stem cell, an epithelial cancer cell, or a tissue containing at least one thereof can be achieved. The cell culture medium of the present invention includes: a Wnt agonist composed of a complex of Wnt protein and afamin, which is a substance capable of stabilizing the Wnt protein, and R-spondin; and at least one selected from the group consisting of a mitogenic growth factor, a bone morphogenetic protein (BMP) inhibitor, a transforming growth factor-β (TGF-β) inhibitor, and a p38 inhibitor.

  本发明提供了一种细胞培养基，用它可以实现上皮干细胞、上皮癌细胞或含有其中至少一种细胞的组织的无血清长期培养。本发明的细胞培养基包括：Wnt 激动剂，由 Wnt 蛋白和阿法明（一种能够稳定 Wnt 蛋白的物质）的复合物以及 R-spondin 组成；以及至少一种选自有丝分裂生长因子、骨形态发生蛋白（BMP）抑制剂、转化生长因子-β（TGF-β）抑制剂和 p38 抑制剂组的物质。
• CELL CULTURE MEDIUM FOR CULTURING ORGANOID, CULTURE METHOD, AND ORGANOID
  申请人：Keio University

  公开号：EP3460042A1

  公开（公告）日：2019-03-27

  A cell culture medium for culturing organoid containing at least two types of components selected from the group consisting of insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2) and epiregulin (EREG), and at least one type of component among the following components i) to iii): i) Wnt agonist, ii) bone morphogenetic protein (BMP) inhibitor, and iii) transforming growth factor-β (TGF-β) inhibitor.

  一种用于培养类器官的细胞培养基，含有至少两种从胰岛素样生长因子 1 (IGF1)、成纤维细胞生长因子 2 (FGF2)和表皮生长因子 (EREG) 组成的组中选出的成分，以及以下成分 i) 至 iii) 中的至少一种成分：i) Wnt 激动剂；ii) 骨形态发生蛋白 (BMP) 抑制剂；iii) 转化生长因子-β (TGF-β) 抑制剂。
• 2D ORGANOID FOR INFECTION AND CULTURE OF HUMAN DIARRHEA VIRUS, AND USE OF SAID 2D ORGANOID
  申请人：Keio University

  公开号：EP3505620A1

  公开（公告）日：2019-07-03

  A 2D organoid for infection and growth culture of human diarrhea virus is obtained by: a step 1 in which a human intestinal epithelial stem cell, a human intestinal epithelial cell, or a tissue containing at least any of these cells is three-dimensionally cultured on an extracellular matrix to obtain a 3D organoid; and a step 2 in which the 3D organoid obtained in the step 1 is dispersed to prepare a single cell, and the single cell is monolayer-cultured on an extracellular matrix to obtain a 2D organoid in which epithelial cells containing differentiated trophoblastic cells and goblet cells and configuring human intestinal lumen have a monolayer structure.

  一种用于人类腹泻病毒感染和生长培养的二维类器官是通过以下方法获得的：步骤1：将人肠上皮干细胞、人肠上皮细胞或至少含有上述任一细胞的组织在细胞外基质上进行三维培养，得到三维类器官；步骤 2：将步骤 1 中获得的三维类器官分散制备单细胞，并将单细胞在细胞外基质上进行单层培养，以获得二维类器官，其中的上皮细胞包含已分化的滋养层细胞和鹅口疮细胞，并配置人体肠腔的单层结构。
• METHOD FOR PREPARING HUMAN HEPATOCYTE PROGENITOR CELLS
  申请人：National Cancer Center

  公开号：EP3533865A1

  公开（公告）日：2019-09-04

  Provided is a method for reprogramming human mature hepatocytes in vitro into liver progenitor cells capable of self-renewal. Disclosed is a method for preparing human liver progenitor cells, comprising culturing human mature hepatocytes in a medium containing serum, A-83-01, and CHIR99021.

  本发明提供了一种在体外将人类成熟肝细胞重编程为能够自我更新的肝祖细胞的方法。本发明公开了一种制备人肝祖细胞的方法，包括在含有血清、A-83-01 和 CHIR99021 的培养基中培养人成熟肝细胞。