Ac-Leu-Gly-Lys-AMC | 660847-12-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Ac-Leu-Gly-Lys-AMC
• 英文别名: (2S)-2-[[2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]acetyl]amino]-6-amino-N-(4-methyl-2-oxochromen-7-yl)hexanamide
• CAS: 660847-12-1
• 化学式: C₂₆H₃₇N₅O₆
• 分子量: 515.61
• InChiKey: DMCYFKPOQPRZCG-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  169
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-乙酰基-L-亮氨酰甘氨酰-N6-乙酰基-N-(4-甲基-2-氧代-2H-1-苯并吡喃-7-基)-L-赖氨酰胺 以 aq. buffer 为溶剂， 反应 1.0h， 生成 Ac-Leu-Gly-Lys-AMC
  参考文献：
  名称：

  锌依赖性赖氨酸脱酰基酶酶的底物分析：HDAC3表现出体外的降糖基化酶活性。

  摘要：

  系统针对一系列荧光底物的11人的锌依赖性赖氨酸脱酰的活动的筛选（参见方案）以及动力学评价揭示基板组蛋白的脱乙酰放映和HDAC10 HDAC11在合理的低的酶浓度。此外，HDAC3在复合体与核受体辅抑制子1（HDAC3-NCoR1）显示窝藏在体外decrotonylase活性。

  DOI：

  10.1002/anie.201203754

文献信息

• A Continuous, Fluorogenic Sirtuin 2 Deacylase Assay: Substrate Screening and Inhibitor Evaluation
  作者：Iacopo Galleano、Matthias Schiedel、Manfred Jung、Andreas S. Madsen、Christian A. Olsen

  DOI：10.1021/acs.jmedchem.5b01532

  日期：2016.2.11

  synthesized fluorogenic substrates enabling enzyme-economical evaluation of SIRT2 inhibitors in a continuous assay format as well as evaluation of the properties of SIRT2 as a long chain deacylase enzyme. Novel enzymatic activities of SIRT2 were thus established in vitro, which warrant further investigation, and two known inhibitors, suramin and SirReal2, were profiled against substrates containing ε-N-acyllysine

  Sirtuins是赖氨酸酰化的重要调节剂，其与细胞代谢和转录控制有关。这使得sirtuin类酶成为开发具有药物潜力的小分子探针的有趣靶标。为了获得有关瑟土因抑制剂的详细分析和动力学见解，重要的是要获得有效的测定方法。在这项工作中，我们报告了易于合成的荧光底物，能够以连续测定形式对SIRT2抑制剂进行酶经济评价，以及对SIRT2作为长链脱酰基酶的特性进行评价。因此，在体外建立了SIRT2的新酶活性，需要进一步研究，并且针对含有ε- N的底物分析了两种已知的抑制剂，苏拉明和SirReal2。-不同长度的酰基赖氨酸修饰。
• CLASS- AND ISOFORM-SPECIFIC HDAC INHIBITORS AND USES THEREOF
  申请人：Mazitschek Ralph

  公开号：US20120208889A1

  公开（公告）日：2012-08-16

  HDAC inhibitors of the general formula (I) and (II) and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase/deacetylase activity as described herein (e.g., cancer). In certain embodiments, the compounds of the invention selectively target either a class or isoform of the HDAC family. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of general formula (IIIc) in the presence of a test compound; and determining the activity of the HDAC protein.

  本文描述的具有一般式（I）和（II）及其药学上可接受的盐的HDAC抑制剂，可用作组蛋白去乙酰化酶或其他去乙酰化酶的抑制剂，并因此可用于治疗与去乙酰化酶/乙酰化酶活性相关的各种疾病和疾病，如本文所述（例如癌症）。在某些实施例中，本发明的化合物有选择性地靶向HDAC家族的一类或同工酶。本发明的另一个方面提供了一种测定试验化合物对HDAC蛋白质抑制作用的测定方法，包括：在试验化合物的存在下，将HDAC蛋白质与一般式（IIIc）的底物孵育，并确定HDAC蛋白质的活性。
• CLASS-AND ISOFORM-SPECIFIC HDAC INHIBITORS AND USES THEREOF
  申请人：President and Fellows of Harvard College

  公开号：US20170267630A1

  公开（公告）日：2017-09-21

  HDAC inhibitors of the general formula (I) and (II) and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase/deacetylase activity as described herein (e.g., cancer). In certain embodiments, the compounds of the invention selectively target either a class or isoform of the HDAC family. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of general formula (IIIc) in the presence of a test compound; and determining the activity of the HDAC protein.
• US8513290B2
  申请人：——

  公开号：US8513290B2

  公开（公告）日：2013-08-20
• US8716344B2
  申请人：——

  公开号：US8716344B2

  公开（公告）日：2014-05-06