L-gamma-谷氨酰-S-{[4-(甲基亚磺酰)丁基]硫代氨基甲酰}-L-半胱氨酰甘氨酸 | 289711-21-3

• 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
• 中文名称: L-gamma-谷氨酰-S-{[4-(甲基亚磺酰)丁基]硫代氨基甲酰}-L-半胱氨酰甘氨酸
• 中文别名: 3-环己烯-1-羧酸,2-氨基-,(1S,2R)-
• 英文名称: sulforaphane glutathione
• 英文别名: D,L-Sulforaphane Glutathione；(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-(4-methylsulfinylbutylcarbamothioylsulfanyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 289711-21-3
• 化学式: C₁₆H₂₈N₄O₇S₃
• 分子量: 484.619
• InChiKey: ROARKYNVUQLTDP-QGQIPBJJSA-N

物化性质

• 熔点：
  157-160°C
• 密度：
  1.444±0.06 g/cm3(Predicted)
• 溶解度：
  可微溶于水（微溶）、甲醇（微溶、加热、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  30
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  265
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  L-gamma-谷氨酰-S-{[4-(甲基亚磺酰)丁基]硫代氨基甲酰}-L-半胱氨酰甘氨酸 以 水 、 二甲基亚砜 为溶剂， 生成 莱菔硫烷 、 谷胱甘肽
  参考文献：
  名称：

  异硫氰酸酯结合物的分解速率决定了它们作为细胞色素p450酶抑制剂的活性。

  摘要：

  异硫氰酸酯（硫醇-ITC）的硫醇共轭物是哺乳动物巯基酸途径中形成的ITC的代谢产物。它们在小鼠肺肿瘤生物测定和其他模型中是有效的化学预防剂。硫醇-ITC是P450的抑制剂，但尚未确定P450的抑制是由于缀合物本身还是由于去共轭反应释放的母体ITC所致。在研究硫醇-ITC的化学预防作用机理时，异硫氰酸苄酯（BITC），苯乙基异硫氰酸酯（PEITC），6-苯基己基异硫氰酸酯（半胱氨酸，半胱氨酸和N-乙酰基-L-半胱氨酸（NAC）缀合物的去偶联率） PHITC）和萝卜硫烷（SFN），表示为一级速率常数k（1）和分解半衰期Dt（1/2），是在pH 7.4和37度的水溶液中测量的。Cys缀合物的Dt（1/2）s比各个GSH缀合物的Dt（1/2）s短几倍，而NAC缀合物的Dt（1/2）s最长。硫醇缀合物的裂解是pH依赖性的，在酸性条件下比在pH 7.4下慢得多。随后对P450 2B1使用PROD（戊氧

  DOI：

  10.1021/tx010029w
• 作为产物：
  描述：

  莱菔硫烷 、 谷胱甘肽 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以53%的产率得到L-gamma-谷氨酰-S-{[4-(甲基亚磺酰)丁基]硫代氨基甲酰}-L-半胱氨酰甘氨酸
  参考文献：
  名称：

  Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo

  摘要：

  The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties. Lead compounds were selected based on potency in a cellular screen and physicochemical properties. Among these, 12 had good aqueous solubility, permeability and long-term solid-state stability at 23 degrees C. Compound 12 also displayed comparable or better efficacy in cellular assays relative to SFN and had in vivo activity in a mouse cigarette smoke challenge model of acute oxidative stress.

  DOI：

  10.1016/j.bmc.2018.12.026

文献信息

• A Comparative Assessment Study of Known Small-Molecule Keap1−Nrf2 Protein–Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity
  作者：Kim T. Tran、Jakob S. Pallesen、Sara M. Ø. Solbak、Dilip Narayanan、Amina Baig、Jie Zang、Alejandro Aguayo-Orozco、Rosa M. C. Carmona、Anthony D. Garcia、Anders Bach

  DOI：10.1021/acs.jmedchem.9b00723

  日期：2019.9.12

  Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance-and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.
• Glucoraphanin and sulforaphane evolution during juice preparation from broccoli sprouts
  作者：Cristiano Bello、Mariateresa Maldini、Simona Baima、Cristina Scaccini、Fausta Natella

  DOI：10.1016/j.foodchem.2018.06.089

  日期：2018.12

  Broccoli sprouts are considered functional food as they are naturally enriched in glucoraphanin (GR) that is the biological precursor of the anticancer compound sulforaphane (SFN). Due to its health promoting value, also broccoli sprout juice is becoming very popular.The present study aimed to quantitatively assess the conversion of GR to its hydrolysis products, SFN and SFN-nitrile, during the juice preparation process. We demonstrated that SFN plus SFN-nitrile yield from glucoraphanin is quite low (approximate to 25%) and that some SFN is lost during the juice preparation partially due to the spontaneous conversion to sulforaphane-amine or conjugation to GSH and proteins naturally present in the juice. Our results demonstrate that the detection of the sole SFN free form does not provide reliable information about the real concentration of this functional compound in the juice.
• Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo
  作者：Jeffrey Boehm、Roderick Davis、Claudia E. Murar、Tindy Li、Brent McCleland、Shuping Dong、Hongxing Yan、Jeffrey Kerns、Christopher J. Moody、Anthony J. Wilson、Alan P. Graves、Mary Mentzer、Hongwei Qi、John Yonchuk、Jen-Pyng Kou、Joseph Foley、Yolanda Sanchez、Patricia L. Podolin、Brian Bolognese、Catherine Booth-Genthe、Marc Galop、Lawrence Wolfe、Robin Carr、James F. Callahan

  DOI：10.1016/j.bmc.2018.12.026

  日期：2019.2

  The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties. Lead compounds were selected based on potency in a cellular screen and physicochemical properties. Among these, 12 had good aqueous solubility, permeability and long-term solid-state stability at 23 degrees C. Compound 12 also displayed comparable or better efficacy in cellular assays relative to SFN and had in vivo activity in a mouse cigarette smoke challenge model of acute oxidative stress.
• Decomposition Rates of Isothiocyanate Conjugates Determine Their Activity as Inhibitors of Cytochrome P450 Enzymes
  作者：C. Clifford Conaway、Jacek Krzeminski、Shantu Amin、Fung-Lung Chung

  DOI：10.1021/tx010029w

  日期：2001.9.1

  isothiocyanates (thiol-ITCs) are metabolites of ITCs formed in the mercapturic acid pathway in mammals. They are effective chemopreventive agents in mouse lung tumor bioassays and in other models. Thiol-ITCs are inhibitors of P450s, but it has not been determined if P450 inhibition is due to conjugates themselves or to parent ITCs released by deconjugation reactions. In studies of mechanism of chemopreventive action

  异硫氰酸酯（硫醇-ITC）的硫醇共轭物是哺乳动物巯基酸途径中形成的ITC的代谢产物。它们在小鼠肺肿瘤生物测定和其他模型中是有效的化学预防剂。硫醇-ITC是P450的抑制剂，但尚未确定P450的抑制是由于缀合物本身还是由于去共轭反应释放的母体ITC所致。在研究硫醇-ITC的化学预防作用机理时，异硫氰酸苄酯（BITC），苯乙基异硫氰酸酯（PEITC），6-苯基己基异硫氰酸酯（半胱氨酸，半胱氨酸和N-乙酰基-L-半胱氨酸（NAC）缀合物的去偶联率） PHITC）和萝卜硫烷（SFN），表示为一级速率常数k（1）和分解半衰期Dt（1/2），是在pH 7.4和37度的水溶液中测量的。Cys缀合物的Dt（1/2）s比各个GSH缀合物的Dt（1/2）s短几倍，而NAC缀合物的Dt（1/2）s最长。硫醇缀合物的裂解是pH依赖性的，在酸性条件下比在pH 7.4下慢得多。随后对P450 2B1使用PROD（戊氧