VK3GS | 29446-72-8

• 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: VK3GS
• 英文别名: 2-methyl-S-glutathionyl-naphthoquinone；thiodione；L-Gamma-Glutamyl-S-(3-Methyl-1,4-Dioxo-1,4-Dihydronaphthalen-2-Yl)-L-Cysteinylglycine；(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-(3-methyl-1,4-dioxonaphthalen-2-yl)sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 29446-72-8
• 化学式: C₂₁H₂₃N₃O₈S
• 分子量: 477.495
• InChiKey: BWKXZXMVXPXYDF-KBPBESRZSA-N

物化性质

• 沸点：
  883.0±65.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  218
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  VK3GS 在 谷胱甘肽 、 recombinant Phanerochaete chrysosporium glutathione transferase Omega isoform 1 、 三羟甲基氨基甲烷盐酸盐 作用下， 以 水 为溶剂， 生成 甲萘醌
  参考文献：
  名称：

  Glutathione Transferases of Phanerochaete chrysosporium

  摘要：

  The white rot fungus Phanerochaete chrysosporium, a saprophytic basidiomycete, possesses a large number of cytosolic glutathione transferases, eight of them showing similarity to the Omega class. PcGSTO1 (subclass I, the bacterial homologs of which were recently proposed, based on their enzymatic function, to constitute a new class of glutathione transferase named S-glutathionyl-(chloro)hydroquinone reductases) and PcGSTO3 (subclass II related to mammalian homologs) have been investigated in this study. Biochemical investigations demonstrate that both enzymes are able to catalyze deglutathionylation reactions thanks to the presence of a catalytic cysteinyl residue. This reaction leads to the formation of a disulfide bridge between the conserved cysteine and the removed glutathione from their substrate. The substrate specificity of each isoform differs. In particular PcGSTO1, in contrast to PcGSTO3, was found to catalyze deglutathionylation of S-glutathionyl-p-hydroquinone substrates. The three-dimensional structure of PcGSTO1 presented here confirms the hypothesis that it belongs not only to a new biological class but also to a new structural class that we propose to name GST xi. Indeed, it shows specific features, the most striking ones being a new dimerization mode and a catalytic site that is buried due to the presence of long loops and that contains the catalytic cysteine.

  DOI：

  10.1074/jbc.m110.194548
• 作为产物：
  描述：

  甲萘醌 、 谷胱甘肽杂质08 以 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 1.0h， 以30%的产率得到VK3GS
  参考文献：
  名称：

  Indoleamine 2,3-Dioxygenase Is the Anticancer Target for a Novel Series of Potent Naphthoquinone-Based Inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. While small molecule inhibitors of IDO exist, there remains a dearth of high-potency compounds offering in vivo efficacy and clinical translational potential. In this study, we address this gap by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the natural product menadione, which is shown in mouse tumor models to have similar antitumor activity to previously characterized IDO inhibitors. Genetic validation that IDO is the critical in vivo target is demonstrated using IDO-null mice. Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar potency inhibitors, including new compounds which are the most potent reported to date (K-i = 61-70 nM). Synthetic accessibility of this class will facilitate preclinical chemical-genetic studies as well as further optimization of pharmacological parameters for clinical translation.

  DOI：

  10.1021/jm7014155