FK228

• 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: FK228
• 英文别名: depsipeptide；Romidepsin (FK228, depsipeptide)；(1R,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone
• 化学式: C₂₄H₃₆N₄O₆S₂
• 分子量: 540.705
• InChiKey: OHRURASPPZQGQM-QSVHVVLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  36
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  193
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  FK228 在 1,4-dithio-D,L-threitol 作用下， 以 acetionitrile 、 水 为溶剂， 生成 (3S,6Z,9S,12R,16R)-6-ethylidene-3,12-di(propan-2-yl)-16-[(E)-4-sulfanylbut-1-enyl]-9-(sulfanylmethyl)-1-oxa-4,7,10,13-tetrazacyclohexadecane-2,5,8,11,14-pentone
  参考文献：
  名称：

  An FAD-Dependent Pyridine Nucleotide-Disulfide Oxidoreductase Is Involved in Disulfide Bond Formation in FK228 Anticancer Depsipeptide

  摘要：

  Disulfide bonds are rare in bacterial natural products, and the mechanism of disulfide bond formation in those products is unknown. Here we characterize a gene and its product critical for a disulfide bond formation in FK228 anticancer depsipeptide in Chromobacterium violaceum. Deletion of depH drastically reduced FK228 production, whereas complementation of the depH-deletion mutant with a copy of depH on a medium copy-number plasmid not only fully restored the FK228 production but also significantly increased the FK228 yield. Purified 6xHis-tagged DepH fusion protein in native form is a homodimer of 71.0 kDa, with each monomer containing one molecule of FAD. DepH efficiently converts an immediate FK228 precursor to FK228 in the presence of NADP+. We conclude that DepH is an FAD-dependent pyridine nucleotide-disulfide oxidoreductase, specifically and efficiently catalyzing a disulfide bond formation in FK228.

  DOI：

  10.1016/j.chembiol.2009.05.005
• 作为产物：
  描述：

  (3S,6Z,9S,12R,16R)-6-ethylidene-3,12-di(propan-2-yl)-16-[(E)-4-sulfanylbut-1-enyl]-9-(sulfanylmethyl)-1-oxa-4,7,10,13-tetrazacyclohexadecane-2,5,8,11,14-pentone 在 FAD-dependent pyridine nucleotide-disulfide oxidoreductase 、 nicotinamide adenine dinucleotide phosphate 、 sodium chloride 作用下， 以 三羟甲基氨基甲烷盐酸盐 为溶剂， 生成 FK228
  参考文献：
  名称：

  An FAD-Dependent Pyridine Nucleotide-Disulfide Oxidoreductase Is Involved in Disulfide Bond Formation in FK228 Anticancer Depsipeptide

  摘要：

  Disulfide bonds are rare in bacterial natural products, and the mechanism of disulfide bond formation in those products is unknown. Here we characterize a gene and its product critical for a disulfide bond formation in FK228 anticancer depsipeptide in Chromobacterium violaceum. Deletion of depH drastically reduced FK228 production, whereas complementation of the depH-deletion mutant with a copy of depH on a medium copy-number plasmid not only fully restored the FK228 production but also significantly increased the FK228 yield. Purified 6xHis-tagged DepH fusion protein in native form is a homodimer of 71.0 kDa, with each monomer containing one molecule of FAD. DepH efficiently converts an immediate FK228 precursor to FK228 in the presence of NADP+. We conclude that DepH is an FAD-dependent pyridine nucleotide-disulfide oxidoreductase, specifically and efficiently catalyzing a disulfide bond formation in FK228.

  DOI：

  10.1016/j.chembiol.2009.05.005

文献信息

• Metabolite derivatives of the HDAC inhibitor FK228
  申请人：Or Sun Yat

  公开号：US20070129290A1

  公开（公告）日：2007-06-07

  The present invention relates to HDAC inhibitor derivatives, particularly derivatives of the free thiol of metabolites of the HDAC inhibitor FK228, pharmaceutical compositions thereof, and to methods of using such derivatives and pharmaceutical compositions thereof in the treatment of diseases associated with HDAC, in particular, tumor or cell proliferation diseases.

  本发明涉及HDAC抑制剂衍生物，特别是FK228的代谢物的游离巯基衍生物，以及其药物组合物，以及使用这些衍生物和药物组合物治疗与HDAC相关的疾病的方法，特别是肿瘤或细胞增殖性疾病。
• METABOLITE DERIVATIVES OF THE HDAC INHIBITOR FK228
  申请人：Or Yat Sun

  公开号：US20110053856A1

  公开（公告）日：2011-03-03

  The present invention relates to HDAC inhibitor derivatives, particularly derivatives of the free thiol of metabolites of the HDAC inhibitor FK228, pharmaceutical compositions thereof, and to methods of using such derivatives and pharmaceutical compositions thereof in the treatment of diseases associated with HDAC, in particular, tumor or cell proliferation diseases.