-联苯]-4-基甲基)-6-苯基-3-(2-吡啶基)-1,2,4-三嗪-5-胺 | 1357171-62-0

• 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 - 苯类化合物 - 苯和取代衍生物
• 中文名称: -联苯]-4-基甲基)-6-苯基-3-(2-吡啶基)-1,2,4-三嗪-5-胺
• 英文名称: ML228
• 英文别名: N-([1,1'-Biphenyl]-4-ylmethyl)-6-phenyl-3-(pyridin-2-yl)-1,2,4-triazin-5-amine；6-phenyl-N-[(4-phenylphenyl)methyl]-3-pyridin-2-yl-1,2,4-triazin-5-amine
• CAS: 1357171-62-0
• 化学式: C₂₇H₂₁N₅
• 分子量: 415.497
• InChiKey: QNRODODTMXCRKU-UHFFFAOYSA-N

物化性质

• 沸点：
  686.0±65.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

生物活性

ML228 (CID-46742353) 是一种有效的 HIF 信号通路激活剂，EC50 值为 1 μM。它不仅能激活 HIF，还能进一步促进下游 EGFR 的活化。

靶点

• EC50: 1 μM (HIF)

体外研究

ML228 (CID-46742353) 是一种新颖的化学类型，为研究 HIF 激活及其治疗潜力提供了宝贵的机会。该化合物在结构上与已知的 HIF 激活剂显著不同，并且缺乏几乎普遍存在于 PHD 抑制剂中的酸性功能团，这可能对于某些疾病应用至关重要。

体内研究

在脊髓损伤 (SCI) 动物模型中，通过注射给予 ML228 (1 μg/kg, 连续 7 天)，能改善局部缺氧和缺血环境，减轻 SCI 的继发性损伤，并促进神经功能的恢复。实验结果显示：

• 动物模型: SD大鼠
• 剂量: 1 μg/kg
• 给药方式: 注射；连续 7 天
• 结果: 缓解了中枢神经系统 SCI 并缓解相关症状。

反应信息

• 作为产物：
  描述：

  2-吡啶氨基腙 在 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 120.17h， 生成 -联苯]-4-基甲基)-6-苯基-3-(2-吡啶基)-1,2,4-三嗪-5-胺
  参考文献：
  名称：

  Discovery of a new molecular probe ML228: An activator of the hypoxia inducible factor (HIF) pathway

  摘要：

  Hypoxia and ischemia are linked to several serious public health problems that affect most major organ systems. Specific examples include diseases of the cardiovascular, pulmonary, renal, neurologic, and musculoskeletal systems. The most significant pathway for cellular response to hypoxia is the hypoxia inducible factor (HIF) pathway. HIFs are transcription factors responsible for the activation of genes which encode proteins that mediate adaptive responses to reduced oxygen availability. A high-throughput cell-based HIF-mediated gene reporter screen was carried out using the NIH's Molecular Libraries Small Molecule Repository to identify activators of the HIF pathway. This communication describes the subsequent medicinal chemistry optimization of a triazine scaffold that led to the identification of the new molecular probe ML228. A discussion of HIF activation SAR within this chemotype as well as detailed in vitro characterization of the probe molecule is presented here. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.077

文献信息

• METHOD FOR PREPARING INDUCED MESENCHYMAL STEM CELLS AND IMPROVING MESENCHYMAL STEM CELL'S CHARACTERS AND ITS APPLICATIONS
  申请人：ACADEMIA SINICA

  公开号：US20180055887A1

  公开（公告）日：2018-03-01

  The present invention generally relates to a method for preparing induced mesenchymal stem cells (iMSCs) and its applications. The iMSCs, like MSCs, can differentiate into multiple lineages, which may be beneficial for disease treatments. In addition, the present invention also provides a method for improving the MSC's functional characteristics such that the MSCs are more suitable for cell therapy or in vitro applications.
• IMPROVED HOMOLOGY DEPENDENT REPAIR GENOME EDITING
  申请人：INARI AGRICULTURE, INC.

  公开号：US20220170034A1

  公开（公告）日：2022-06-02

  Compounds and related reagents, systems, methods, and compositions for increasing the frequency of homology directed repair (HDR) of target genomic sites with genome editing molecules are provided.
• Discovery of a new molecular probe ML228: An activator of the hypoxia inducible factor (HIF) pathway
  作者：Jimmy R. Theriault、Andrew S. Felts、Brittney S. Bates、Jose R. Perez、Michelle Palmer、Shawn R. Gilbert、Eric S. Dawson、Julie L. Engers、Craig W. Lindsley、Kyle A. Emmitte

  DOI：10.1016/j.bmcl.2011.11.077

  日期：2012.1

  Hypoxia and ischemia are linked to several serious public health problems that affect most major organ systems. Specific examples include diseases of the cardiovascular, pulmonary, renal, neurologic, and musculoskeletal systems. The most significant pathway for cellular response to hypoxia is the hypoxia inducible factor (HIF) pathway. HIFs are transcription factors responsible for the activation of genes which encode proteins that mediate adaptive responses to reduced oxygen availability. A high-throughput cell-based HIF-mediated gene reporter screen was carried out using the NIH's Molecular Libraries Small Molecule Repository to identify activators of the HIF pathway. This communication describes the subsequent medicinal chemistry optimization of a triazine scaffold that led to the identification of the new molecular probe ML228. A discussion of HIF activation SAR within this chemotype as well as detailed in vitro characterization of the probe molecule is presented here. (C) 2011 Elsevier Ltd. All rights reserved.