6-bromoindirubin 3’-oxime | 710323-58-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-bromoindirubin 3’-oxime
• 英文别名: 6-bromoindirubin-3'-oxime；6-bromoindirubin-3’-oxime；BIO；6-bromoindirubin-3'-monoxime
• CAS: 710323-58-3
• 化学式: C₁₆H₁₀BrN₃O₂
• 分子量: 356.178
• InChiKey: DDLZLOKCJHBUHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  22.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.72
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  6-bromoindirubin 3’-oxime 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以100 %的产率得到(2Z,3E)-6'-bromo-3-(hydroxyimino)-[2,3'-biindolinylidene]-2'-one lithium salt
  参考文献：
  名称：

  [EN] INDIRUBIN COMPOUNDS AND METHODS THEREOF
  [FR] COMPOSÉS D'INDIRUBINE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  The present disclosure discloses a compound of Formula I and the process of preparation thereof. The present disclosure discloses indirubin compounds of Formula I which are potent inducers of autophagy. The present disclosure also discloses a pharmaceutical composition comprising compound of Formula I and methods thereof.

  公开号：

  WO2022229986A1
• 作为产物：
  描述：

  吲哚乙酸酯 在 吡啶 、 盐酸羟胺 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 6-bromoindirubin 3’-oxime
  参考文献：
  名称：

  The Indirubin Derivative 6-Bromoindirubin-3′-Oxime Activates Proteostatic Modules, Reprograms Cellular Bioenergetic Pathways, and Exerts Antiaging Effects

  摘要：

  Aims: Organismal aging can be delayed by mutations that either activate stress responses or reduce the nutrient-sensing pathway signaling; thus, by using Drosophila melanogaster as an in vivo experimental screening platform, we searched for compounds that modulate these pathways.Results: We noted that oral administration of the glycogen synthase kinase 3 (Gsk-3) inhibitor 6-bromoindirubin-3-oxime (6BIO) in Drosophila flies extended healthy life span. 6BIO is not metabolized in fly tissues, modulated bioenergetic pathways, decreased lipid and glucose tissue load, activated antioxidant and proteostatic modules, and enhanced resistance to stressors. Mechanistically, we found that the effects on the stress-responsive pathways were largely dependent on the activity of the transcription factor nuclear factor erythroid 2-related factor (Nrf-2). Genetic inhibition of Gsk-3 largely phenocopied the 6BIO-mediated effects, while high levels of Gsk-3 expression and/or kinase activity suppressed proteostatic modules and reduced flies' longevity; these effects were partially rescued by 6BIO. Also, 6BIO was found to partially reduce the 3-phosphoinositide-dependent protein kinase-1 (Pdpk1) activity, a major effector of the insulin/insulin-like growth factor-1 cell signaling pathways.Innovation: 6BIO exerts the unique property of increasing stress tolerance and in parallel partially suppressing the nutrient-sensing pathway signaling.Conclusion: Our findings suggest that the 6BIO scaffold can be used for the development of novel antiaging compounds.

  DOI：

  10.1089/ars.2016.6910

文献信息

• Indirubin derivatives protect against endoplasmic reticulum stress-induced cytotoxicity and down-regulate CHOP levels in HT22 cells
  作者：Yasuhiro Kosuge、Hiroaki Saito、Tatsuki Haraguchi、Yoshimi Ichimaru、Sachiyo Ohashi、Hiroko Miyagishi、Shunsuke Kobayashi、Kumiko Ishige、Shinichi Miyairi、Yoshihisa Ito

  DOI：10.1016/j.bmcl.2017.10.069

  日期：2017.12

  Indirubin and its derivatives have been reported to exhibit anti-cancer and anti-inflammatory activities. Recently, some of its derived analogs have been shown to have neuroprotective potential. Endoplasmic reticulum (ER) stress has been demonstrated to contribute to the pathogenesis of various neurodegenerative diseases, whereas the effects of indirubin derivatives on ER stress-induced cell death

  据报道，靛玉红及其衍生物表现出抗癌和抗炎活性。最近，一些衍生的类似物已显示具有神经保护潜力。内质网（ER）应激已被证明有助于各种神经退行性疾病的发病机理，而靛玉红衍生物对ER应激诱导的细胞死亡的影响尚未得到解决。在本研究中，准备了一系列靛玉红的44种衍生物，以寻找针对ER应激引起的神经元死亡的新型神经保护剂。MTT降低试验表明，内质网应激的诱导剂衣霉素（TM）显着降低了海马神经元HT22细胞的活力。在测试的化合物中，有八种显示出对TM诱导的细胞死亡的显着抑制活性。蛋白质印迹分析表明，将这些类似物与TM同时应用于细胞会降低TM诱导的CHOP的表达，而CHOP是ER应激的既定介质。我们的结果表明，这些靛玉红衍生物对内质网应激诱导的神经元死亡的预防作用可能至少部分是由于CHOP依赖性信号传导系统的减弱。
• COMPOUNDS TO TREAT HEARING LOSS
  申请人：Fate Therapeutics, Inc.

  公开号：US20150126507A1

  公开（公告）日：2015-05-07

  The invention is directed, in part, to compounds of structure (I) to treat or prevent hearing loss. Compounds of the present invention also promote sensory hair cell regeneration. Particular compositions comprise compounds of structure (I), and optionally one or more small molecules that increase the proliferation of supporting cells.

  本发明部分涉及结构式(I)的化合物，用于治疗或预防听力损失。本发明的化合物还促进感觉毛细胞再生。特定的组合物包括结构式(I)的化合物，以及可选地增加支持细胞增殖的一个或多个小分子。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• Mammalian neural plate border stem cells capable of forming neural tube and neural crest cell lineages including central and peripheral neurons
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2614829A1

  公开（公告）日：2013-07-17

  The present invention relates to a method for producing mammalian neural plate border stem cells (NPBSCs), comprising: (a) differentiation of mammalian pluripotent stem cells by (a-i) culturing mammalian pluripotent stem cells in pluripotent stem cell medium for about 24 to about 96 hours, wherein the pluripotent stem cell medium comprises: (i) an inhibitor of the activin/TGF-β signalling pathway; (ii) an inhibitor of the BMP signalling pathway; (iii) an activator of the canonical WNT signalling pathway; and (iv) an activator of the Hedgehog signalling pathway; subsequently (a-ii) culturing the cells obtained in step (a-i) for about 24 to about 96 hours in a neural medium, wherein the neural medium comprises: (i) an inhibitor of the Activin/TGF-β signalling pathway; (ii) an inhibitor of the BMP signalling pathway; (iii) an activator of the canonical WNT signalling pathway; and (iv) an activator of the Hedgehog signalling pathway; subsequently (a-iii) culturing the cells obtained in step (a-ii) for about 24 to about 96 hours in a neural medium, wherein the neural medium comprises: (i) an activator of the canonical WNT signalling pathway; (ii) an activator of the Hedgehog signalling pathway; and (iii) an inhibitor of oxidation; and (b) plating the obtained differentiated mammalian pluripotent stem cells in NPBSCs expansion medium, wherein the NPBSCs expansion medium comprises (i) an activator of the canonical WNT signalling pathway; (ii) an activator of the Hedgehog signalling pathway; and (iii) an inhibitor of oxidation; and expanding the cells in the NPBSCs expansion medium for about 24 to about 96 hours; (c) splitting the cells obtained in (b) and further expanding the cells in the NPBSCs expansion medium; and (d) repeating step (c) at least two times. The present invention further relates to neural plate border stem cells obtainable by the method of the invention and the use of the cells of the invention in medicine.

  本发明涉及一种生产哺乳动物神经板边缘干细胞（NPBSCs）的方法，包括：(a)哺乳动物多能干细胞的分化，方法是(a-i)将哺乳动物多能干细胞在多能干细胞培养基中培养约24至约96小时，其中多能干细胞培养基包括：(i)激活素/TGF-β信号通路的抑制剂；(ii)BMP信号通路的抑制剂；(iii)典型WNT信号通路的激活剂：(i)活化素/TGF-β信号通路的抑制剂；(ii)BMP信号通路的抑制剂；(iii)典型WNT信号通路的激活剂；以及(iv)刺猬信号通路的激活剂；随后(a-ii)将步骤(a-i)中获得的细胞在神经培养基中培养约24至约96小时，其中神经培养基包括：(i)Activin/TGF-β信号通路的抑制剂；(ii)BMP信号通路的抑制剂；(iii)典型WNT信号通路的激活剂；和(iv)刺猬信号通路的激活剂；随后(a-iii)将步骤(a-ii)中获得的细胞在神经培养基中培养约24至约96小时，其中神经培养基包括：(i)典型 WNT 信号通路的激活剂；(ii)刺猬信号通路的激活剂；和(iii)氧化抑制剂；和(b)将获得的分化哺乳动物多能干细胞在 NPBSCs 扩增培养基中培养，其中 NPBSCs 扩增培养基包括：(i)典型 WNT 信号通路的激活剂；(ii) Hedgehog 信号通路的激活剂；和 (iii) 氧化抑制剂；并将细胞在 NPBSCs 扩增培养基中扩增约 24 至约 96 小时； (c) 分裂(b)中获得的细胞并进一步将细胞在 NPBSCs 扩增培养基中扩增；和 (d) 重复步骤(c)至少两次。本发明进一步涉及通过本发明方法获得的神经板边缘干细胞以及本发明细胞在医学中的应用。
• Methods and compositions for producing hepatocyte-like cells
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10004767B2

  公开（公告）日：2018-06-26

  Methods are provided for producing a population of hepatocyte-like cells (iHeps) from a population of adipocyte-derived stem cells (ASCs). Aspects of the methods include placing a population of ASCs into a three dimensional culture (e.g., hanging drop suspension culture, high density culture, spinner flask culture, microcarrier culture, etc.), and contacting the cells with a first and second culture medium. Also provided are methods of treating an individual, which include producing a population of iHeps from a population of ASCs, and administering an effective number of iHeps into the individual. Kits for practicing the methods are also described herein.

  本文提供了从脂肪细胞衍生干细胞（ASCs）群体中产生肝细胞样细胞（iHeps）的方法。这些方法的各个方面包括将ASCs群体放入三维培养（例如，悬滴悬浮培养、高密度培养、旋转瓶培养、微载体培养等）中，并使细胞与第一和第二培养基接触。还提供了治疗个体的方法，其中包括从 ASCs 群体中产生 iHeps 群体，并向个体施用有效数量的 iHeps。本文还描述了用于实施这些方法的试剂盒。