thailandepsin A

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: thailandepsin A
• 英文别名: burkholdac B；TDP-A；(1S,5S,6R,9S,15E,20R)-6-butan-2-yl-5-hydroxy-20-(2-methylsulfanylethyl)-2-oxa-11,12-dithia-7,19,22-triazabicyclo[7.7.6]docos-15-ene-3,8,18,21-tetrone
• 化学式: C₂₃H₃₇N₃O₆S₃
• 分子量: 547.761
• InChiKey: VJXBYUITQBTTQM-KOKRHUQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  210
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  thailandepsin A 在 Cleland's reagent 作用下， 生成
  参考文献：
  名称：

  Thailandepsins: Bacterial Products with Potent Histone Deacetylase Inhibitory Activities and Broad-Spectrum Antiproliferative Activities

  摘要：

  Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer drugs, with one synthetic compound, SAHA (vorinostat, Zolinza; 1), and one natural product, FK228 (depsipeptide, romidepsin, Istodax; 2), approved by FDA for clinical use. Our studies of FK228 biosynthesis in Chromobacterium violaceum no. 968 led to the identification of a cryptic biosynthetic gene cluster in the genome of Burkholderia thailandensis E264. Genome mining and genetic manipulation of this gene cluster further led to the discovery of two new products, thailandepsin A (6) and thailandepsin B (7). HDAC inhibition assays showed that thailandepsins have selective inhibition profiles different from that of FK228, with comparable inhibitory activities to those of FK228 toward human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC9 but weaker inhibitory activities than FK228 toward HDAC4 and HDAC8, the latter of which could be beneficial. NCI-60 anticancer screening assays showed that thailandepsins possess broad-spectrum antiproliferative activities with GI(50) for over 90% of the tested cell lines at low nanomolar concentrations and potent cytotoxic activities toward certain types of cell lines, particularly for those derived from colon, melanoma, ovarian, and renal cancers. Thailandepsins thus represent new naturally produced HDAC inhibitors that are promising for anticancer drug development.

  DOI：

  10.1021/np200324x

文献信息

• [EN] NOVEL HDAC INHIBITORS AND METHODS OF TREATMENT USING THE SAME<br/>[FR] NOUVEAUX INHIBITEURS DE HDAC ET MÉTHODES D'UTILISATION DE CES DERNIERS
  申请人：UWM RES FOUND INC

  公开号：WO2017039726A1

  公开（公告）日：2017-03-09

  Disclosed herein are novel HDAC inhibitors. The HDAC inhibitors may be used in methods of treating cancer. The HDAC inhibitors may be used in methods of treating a neurological disorder.

  本文披露了新型HDAC抑制剂。这些HDAC抑制剂可用于治疗癌症的方法。这些HDAC抑制剂可用于治疗神经系统疾病的方法。
• HDAC inhibitors and methods of treatment using the same
  申请人：UWM Research Foundation, Inc.

  公开号：US11149062B2

  公开（公告）日：2021-10-19

  Disclosed herein are novel HDAC inhibitors. The HDAC inhibitors may be used in methods of treating cancer. The HDAC inhibitors may be used in methods of treating a neurological disorder.

  本文公开了新型 HDAC 抑制剂。这些 HDAC 抑制剂可用于治疗癌症的方法。HDAC 抑制剂可用于治疗神经系统疾病的方法。