4-MUG

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4-MUG
• 英文别名: (2S,3S,4S,5R)-3,4,5-trihydroxy-6-(4-methyl-2-oxochromen-7-yl)oxyoxane-2-carboxylic acid
• 化学式: C₁₆H₁₆O₉
• 分子量: 352.298
• InChiKey: ARQXEQLMMNGFDU-AKFOCJAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  羟甲香豆素 、 UDP-glucuronic acid 在 human UDP-glucuronosyltransferase 1A₉ 、 magnesium chloride 、 alamethicin 、 糖质酸-1,4-内酯 作用下， 生成 4-MUG
  参考文献：
  名称：

  Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches

  摘要：

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。

  DOI：

  10.1007/s11095-012-0666-z

文献信息

• Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches
  作者：Baojian Wu、Xiaoqiang Wang、Shuxing Zhang、Ming Hu

  DOI：10.1007/s11095-012-0666-z

  日期：2012.6

  Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2  = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2  = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。
• [EN] AN ESTERIFICATION/SAPONIFICATION-BASED METHOD FOR LIPOSOMAL LOADING<br/>[FR] PROCÉDÉ À BASE D'ESTÉRIFICATION/SAPONIFICATION POUR CHARGEMENT LIPOSOMAL
  申请人：ACADEMIA SINICA

  公开号：WO2017120190A1

  公开（公告）日：2017-07-13

  Described herein is a method for loading a hydrophilic compound into liposomes after addition of an alkylester group to form an esterified compound. After loading, the alkylester is hydrolyzed to reform the hydrophilic compound inside the liposomes. Also described is a method for loading drugs under a glucuronide methylester form into liposomes. The glucuronide methylester form of the drug is saponified to a glucuronide form of the drug inside the liposomes for better drug retention. The glucuronide residue conjugated to drugs can be removed inside cells to regenerate the parental drug upon cell uptake, liposomal degradation and enzyme hydrolysis. In case of cancer, this method can be used to safely deliver drugs to tumors.

  本文描述了一种将亲水化合物加载到脂质体中的方法，方法是在加入烷基酯基团后形成酯化化合物。加载后，烷基酯被水解以重新在脂质体内形成亲水化合物。还描述了一种将药物以葡萄糖醛酸甲酯形式加载到脂质体中的方法。将药物的葡萄糖醛酸甲酯形式皂化为脂质体内药物的葡萄糖醛酸形式，以增强药物的保留。与药物结合的葡萄糖醛酸残基可以在细胞内去除，从而在细胞摄取、脂质体降解和酶水解过程中再生母药。在癌症情况下，这种方法可用于安全地将药物输送到肿瘤中。
• Interaction of bisphenol a with human UDP-glucuronosyltransferase 1A6 enzyme
  作者：Nobumitsu Hanioka、Yuri Takeda、Toshiko Tanaka-Kagawa、Keiko Hayashi、Hideto Jinno、Shizuo Narimatsu

  DOI：10.1002/tox.20345

  日期：2008.6

  The effects of bisphenol A (BPA) on UDP‐glucuronosyltransferase 1A6 (UGT1A6) activities in microsomes from human livers and yeast cells expressing human UGT1A6 (humUGT1A6) were investigated. Serotonin (5‐HT) and 4‐methylumbelliferone (4‐MU) were used as the substrates for UGT1A6. BPA dose‐dependently inhibited 5‐HT and 4‐MU glucuronidation activities in both enzyme sources. The IC50 values of BPA for

  研究了双酚 A (BPA) 对来自人类肝脏和表达人类 UGT1A6 (humUGT1A6) 的酵母细胞微粒体中 UDP-葡萄糖醛酸基转移酶 1A6 (UGT1A6) 活性的影响。血清素 (5-HT) 和 4-甲基伞形酮 (4-MU) 被用作 UGT1A6 的底物。BPA 剂量依赖性地抑制两种酶源中的 5-HT 和 4-MU 葡萄糖醛酸化活性。BPA 对 5-HT 和 4-MU 葡萄糖醛酸化活性的 IC50 值对于肝微粒体分别为 156 和 163 μM，对于表达 humUGT1A6 的酵母细胞微粒体分别为 84.6 和 80.3 μM。BPA 对人肝微粒体中 5-HT 和 4-MU 葡萄糖醛酸化活性的抑制模式表现出竞争性和非竞争性成分的混合物，Ki 值分别为 84.9 和 72.3 μM。在表达 humUGT1A6 的酵母细胞微粒体中，BPA 非竞争性抑制 5-HT 葡萄糖醛酸化活性（Ki
• [EN] FLUOROGENIC OR FLUOROPHORIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS FLUOROGÈNES OU FLUOROPHORES ET UTILISATIONS DE CEUX-CI
  申请人：3M INNOVATIVE PROPERTIES CO

  公开号：WO2012134724A1

  公开（公告）日：2012-10-04

  Compounds are provided that are either fluorogenic or fluorophoric. Compositions and articles that include the compounds are also provided. Additionally, methods of detecting a microorganism using the compounds are provided. The compounds are fluorinated and can be used advantageously under acidic conditions.

  提供了既具有荧光基团又具有荧光性质的化合物。还提供了包含这些化合物的组合物和物品。此外，还提供了利用这些化合物检测微生物的方法。这些化合物是氟化的，并且可以在酸性条件下有优势地使用。
• [EN] PHENOXY THIOPHENE SULFONAMIDES AND THEIR USE AS INHIBITORS OF GLUCURONIDASE<br/>[FR] PHÉNOXYTHIOPHÈNESULFAMIDES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA GLUCURONIDASE
  申请人：UNIV NORTH CAROLINA

  公开号：WO2011112858A1

  公开（公告）日：2011-09-15

  This invention relates generally to compounds that are glucuronidase inhibitors. Glucuronidase inhibitors described include phenoxy thiophene sulfonamides. Other compounds, for instance pyridine sulfonyls, benzene sulfonyls, thiophene sulfonyls, thiazole sulfonyls, thiophene carbonyls, and thiazole carbonyls, are also contemplated. Also contemplated are compositions including one or more of such compounds for use inhibiting glucuronidase and methods of using one or more of such compounds as a co-drug to be used in combination with the anticancer drug CPT-11.

  本发明涉及一般与葡萄糖醛酸酶抑制剂有关的化合物。所描述的葡萄糖醛酸酶抑制剂包括苯氧基噻吩磺酰胺。其他化合物，例如吡啶磺酰基、苯磺酰基、噻吩磺酰基、噻唑磺酰基、噻吩羰基和噻唑羰基也被考虑在内。还考虑包括一种或多种此类化合物的组合物，用于抑制葡萄糖醛酸酶，并使用一种或多种此类化合物作为联合用药，与抗癌药物CPT-11一起使用的辅助药物。