(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-hydroxy-9-methyl-11-(methylamino)-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3′,2′,1′-lm]pyrrolo[3,4-j][1,7]-benzodiazonin-1-one

• 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: (9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-hydroxy-9-methyl-11-(methylamino)-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3′,2′,1′-lm]pyrrolo[3,4-j][1,7]-benzodiazonin-1-one
• 英文别名: 3'-Demethoxy-3'-hydroxystaurosporine；3'-Demethylstaurosporine；(2S,3R,4R,6R)-3-hydroxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one
• 化学式: C₂₇H₂₄N₄O₃
• 分子量: 452.513
• InChiKey: YFYYWLWHOINTHH-FCHZLITKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  80.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯甲酸酐 、 (9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-hydroxy-9-methyl-11-(methylamino)-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3′,2′,1′-lm]pyrrolo[3,4-j][1,7]-benzodiazonin-1-one 以 乙醇 为溶剂， 反应 0.75h， 以33%的产率得到N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-hydroxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3′,2′,1′-lm]pyrrolo[3,4-j][1,7]benzodiazonin-11-yl]-N-methylbenzamide
  参考文献：
  名称：

  Comparison of the Kinase Profile of Midostaurin (Rydapt) with That of Its Predominant Metabolites and the Potential Relevance of Some Newly Identified Targets to Leukemia Therapy

  摘要：

  多靶点蛋白激酶抑制剂米哚妥林被批准用于治疗新诊断的FLT3突变急性髓性白血病（AML）和KIT驱动的晚期系统性肥大细胞增多症。急性髓细胞白血病是一种异质性恶性肿瘤，针对FLT3的研究药物在FLT3突变急性髓细胞白血病患者中显示出不同的疗效，这可能是由于这些药物在给药剂量下抑制了不同的靶点和途径。然而，药物的疗效和副作用并不仅仅反映了母体化合物的生化和药效学特性，往往还包括母体和活性代谢物之间复杂的协同作用。长期用药后，两种米哚妥林代谢物的稳态血浆谷值水平高于母药。在这项研究中，我们对这些代谢物进行了特征描述，并使用放射性转磷酸化测定法确定了它们作为激酶抑制剂的特性。与米哚妥林一样，这些代谢物也能有效抑制突变形式的 FLT3 和 KIT 以及其他几种激酶，这些激酶要么直接参与了失调的信号通路，要么被认为通过基质支持在急性髓细胞性白血病中发挥作用，如 IGF1R、LYN、PDPK1、RET、SYK、TRKA 和 VEGFR2。因此，midostaurin 及其代谢物的激酶活性之间的复杂相互作用很可能有助于midostaurin在急性髓细胞性白血病中的疗效，并有助于使该药物在这种恶性肿瘤中产生与其他FLT3抑制剂不同的效果。

  DOI：

  10.1021/acs.biochem.8b00727

文献信息

• Methods for conducting assays for enzyme activity on protein microarrays
  申请人：Zhou X. Fang

  公开号：US20050118665A1

  公开（公告）日：2005-06-02

  The present invention relates to methods of conducting assays for enzymatic activity on microarrays useful for the large-scale study of protein function, screening assays, and high-throughput analysis of enzymatic reactions. The invention relates to methods of using protein chips to assay the presence, amount, activity and/or function of enzymes present in a protein sample on a protein chip. In particular, the methods of the invention relate to conducting enzymatic assays using a microarray wherein a protein and a substance are immobilized on the surface of a solid support and wherein the protein and the substance are in proximity to each other sufficient for the occurrence of an enzymatic reaction between the substance and the protein. The invention also relates to microarrays that have an enzyme and a substrate immobilized on their surface wherein the enzyme and the substrate are in proximity to each other sufficient for the occurrence of an enzymatic reaction between the enzyme and the substrate.

  本发明涉及在微阵列上进行酶活性测定的方法，这种方法可用于蛋白质功能的大规模研究、筛选测定和酶反应的高通量分析。本发明涉及使用蛋白质芯片检测蛋白质芯片上蛋白质样品中酶的存在、数量、活性和/或功能的方法。特别是，本发明的方法涉及使用芯片进行酶测定，其中蛋白质和物质被固定在固体支持物表面，蛋白质和物质相互靠近，足以使物质和蛋白质之间发生酶反应。本发明还涉及在其表面固定有酶和底物的微阵列，其中酶和底物相互靠近，足以使酶和底物之间发生酶反应。
• Nucleic Acids and Proteins and Methods for Making and Using Them
  申请人：Mathur Eric J.

  公开号：US20100011456A1

  公开（公告）日：2010-01-14

  The invention provides polypeptides, including enzymes, structural proteins and binding proteins, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. Polypeptides, including enzymes and antibodies, and nucleic acids of the invention can be used in industrial, experimental, food and feed processing, nutritional and pharmaceutical applications, e.g., for food and feed supplements, colorants, neutraceuticals, cosmetic and pharmaceutical needs.
• NUCLEIC ACIDS AND PROTEINS AND METHODS FOR MAKING AND USING THEM
  申请人：Chang Hwai

  公开号：US20110296543A1

  公开（公告）日：2011-12-01

  The invention provides polypeptides, including enzymes, structural proteins and binding proteins, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. Polypeptides, including enzymes and antibodies, and nucleic acids of the invention can be used in industrial, experimental, food and feed processing, nutritional and pharmaceutical applications, e.g., for food and feed supplements, colorants, neutraceuticals, cosmetic and pharmaceutical needs. Polypeptides of the invention can be used in food processing, brewing, bath additives, alcohol production, peptide synthesis, enantioselectivity, hide preparation in the leather industry, waste management and animal degradation, silver recovery in the photographic industry, medical treatment, silk degumming, biofilm degradation, biomass conversion to a biofuel (e.g., a bioethanol, biomethanol, biopropanol or biobutanol, a biodiesel, etc.), biodefense, antimicrobial agents and disinfectants, personal care and cosmetics, biotech reagents, in corn wet milling and pharmaceuticals such as digestive aids and anti-inflammatory (anti-phlogistic) agents.
• US7635572B2
  申请人：——

  公开号：US7635572B2

  公开（公告）日：2009-12-22
• US8119385B2
  申请人：——

  公开号：US8119385B2

  公开（公告）日：2012-02-21