N-(2-氨基乙基)-5-氯异喹啉-8-磺酰胺双盐酸盐 | 1177141-67-1

• 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: N-(2-氨基乙基)-5-氯异喹啉-8-磺酰胺双盐酸盐
• 中文别名: N-(2-氨基乙基)-5-氯异喹啉-8-磺酰胺二盐酸盐；CKI-7盐酸盐
• 英文名称: N-(2-Aminoethyl)-5-chloroisoquinoline-8-sulfonamide dihydrochloride
• 英文别名: N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide;dihydrochloride
• CAS: 1177141-67-1
• 化学式: C11H14Cl3N3O2S
• 分子量: 358.7
• InChiKey: JUAVTXYOCISSSL-UHFFFAOYSA-N

物化性质

• 熔点：
  187-189°C
• 溶解度：
  在水中的溶解度>5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  93.5
• 氢给体数：
  4
• 氢受体数：
  5

制备方法与用途

生物活性

CKI-7 是一种有效且 ATP 竞争性的酪蛋白激酶 1 (CK1) 抑制剂，IC50 为 6 μM，Ki 为 8.5 μM。CKI-7 选择性抑制 Cdc7 激酶，还抑制 SGK，S6K1 以及 MSK1。CKI-7 对酪蛋白激酶 II 和其他蛋白激酶的作用弱得多。

靶点

CK1 6 μM (IC 50 )

CK1 8.5 μM (Ki)

Cdc7

SGK

S6K1

MSK1

体外研究

CKI-7 (0.1-10 μM; 5 days; ES cells) treatment significantly increases the expression of the early neuroectodermal marker Sox1 and the number of cells positive for the neural markers nestin and βIII-tubulin, in a concentration-dependent manner.
CKI-7 (5 μM; 5 days; ES cells) treatment suppresses SFEB-induced β-catenin stabilization on day 5, indicating that CKI-7 inhibits Wnt signaling.

RT-PCR

Cell Line:	Mouse ES cells
Concentration:	0.1-10 μM
Incubation Time:	5 days
Result:	Significantly increased the expression of the early neuroectodermal marker Sox1 and the number of cells positive for the neural markers nestin and βIII-tubulin, in a concentration-dependent manner.

Western Blot Analysis

Cell Line:	Mouse ES cells
Concentration:	5 μM
Incubation Time:	5 days
Result:	Suppressed SFEB-induced β-catenin stabilization on day 5.

体内研究

In vivo dose-dependent anti-tumor activity of CKI-7 is demonstrated in a SCID-Beige mouse systemic tumor model utilzing a recently isolated Philadelphia chromosome positive acute lymphoblastic leukemia cell line. Standard cell cycle synchronization studies established that exposure to CKI-7 results in cell cycle dependent caspase 3 activation and apoptotic cell death.

文献信息

• Method for generating Retinal Pigment Epithelium (RPE) cells from Induced Pluripotent Stem Cells (IPSCs)
  申请人：THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services

  公开号：US10480031B2

  公开（公告）日：2019-11-19

  High efficiency methods for producing retinal pigment epithelial cells from induced pluripotent stem cells (iPSCs) are disclosed herein. The iPSCs are produced from somatic cells, including retinal pigment epithelial (RPE) cells, such as fetal RPE stem cells. In some embodiments, the iPSC include a tyrosinase promoter operably linked to a marker. Methods are disclosed for using the RPE cells, such as for treatment. Methods for screening for agents that affect RPE differentiation are also disclosed.

  本文公开了利用诱导多能干细胞（iPSC）生产视网膜色素上皮细胞的高效方法。iPSC 由体细胞产生，包括视网膜色素上皮（RPE）细胞，如胎儿 RPE 干细胞。在某些实施方案中，iPSC 包括与标记可操作连接的酪氨酸酶启动子。公开了使用 RPE 细胞的方法，例如用于治疗的方法。还公开了筛选影响RPE分化的药物的方法。
• MACS-based purification of stem cell-derived retinal pigment epithelium
  申请人：FUJIFILM Cellular Dynamics, Inc.

  公开号：US11162070B2

  公开（公告）日：2021-11-02

  Provided herein are methods of enriching a retinal pigment epithelium (RPE) cell population derived from stem cells. Such a method may comprise removing contaminating cells through the depletion of CD24 positive cells, CD56 positive cells, and/or CD90 positive cells from a starting population of RPE cells.

  本文提供了富集源自干细胞的视网膜色素上皮（RPE）细胞群的方法。这种方法可包括从RPE细胞起始群体中去除CD24阳性细胞、CD56阳性细胞和/或CD90阳性细胞，从而去除污染细胞。
• METHOD FOR GENERATING RETINAL PIGMENT EPITHELIUM (RPE) CELLS FROM INDUCED PLURIPOTENT STEM CELLS (IPSCs)
  申请人：The United States of America, as represented by The Secretary, Department of Health and Human Services

  公开号：EP2951290A2

  公开（公告）日：2015-12-09
• METHOD FOR GENERATING RETINAL PIGMENT EPITHELIUM (RPE) CELLS FROM INDUCED PLURIPOTENT STEM CELLS (IPSCS)
  申请人：The United States of America, as represented by The Secretary, Department of Health and Human Services

  公开号：EP2951290B1

  公开（公告）日：2017-11-29
• MACS-BASED PURIFICATION OF STEM CELL-DERIVED RETINAL PIGMENT EPITHELIUM
  申请人：FUJIFILM Cellular Dynamics, Inc.

  公开号：EP3347457A1

  公开（公告）日：2018-07-18