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1. 发明申请

WO2007137255A2 BACTERIAL THIOREDOXIN REDUCTASE INHIBITORS AND METHODS FOR USE THEREOF 审中-公开
标题翻译：细菌三氧化二氮还原酶抑制剂及其使用方法
公开(公告)号：WO2007137255A2
公开(公告)日：2007-11-29
申请号：PCT/US2007069455
申请日：2007-05-22
申请人： THIOREDOXIN SYSTEMS AB , THYOGEN PHARMACEUTICALS INC , HOLMGREN ARNE , LU JUN , VLAMIS-GARDIKAS ALEXIOS , ZHAO RONG , KANDASAMY K , ENGMAN LARS , ENGSTRAND LARS , HOFFNER SVEN
发明人： HOLMGREN ARNE , LU JUN , VLAMIS-GARDIKAS ALEXIOS , ZHAO RONG , KANDASAMY K , ENGMAN LARS , ENGSTRAND LARS , HOFFNER SVEN
IPC分类号： A61K31/41
CPC分类号： C07D421/04 , A61K31/381 , A61K31/41 , C07D293/12
摘要： The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E.coli TrxR with K i of 0.14 µM and 0.46 µM, respectively. E.coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains. Two major pathogenic bacteria, which previously had not been known to be sensitive to ebselen, Mycobacterium tuberculosis (tuberculosis) and Helicobacter pylori (stomach ulcer and cancer), were shown to be excellent targets. Helicobacter
摘要翻译： Ebselen的作用机制区分细菌和哺乳动物硫氧还蛋白还原酶（TrxR）。它显示哺乳动物Trx的快速氧化，并且通过NADPH-TrxR催化依次硒硒酚与过氧化氢的周转，因此是哺乳动物抗氧化剂。依布硒及其二硒化物是分别具有0.14μM和0.46μM的KI大肠杆菌TrxR的强竞争性抑制剂。缺乏谷胱甘肽还原酶或谷胱甘肽的大肠杆菌突变体对依贝硒的抑制更敏感。由于谷氧还蛋白或硫氧还蛋白系统是核糖核苷酸还原酶的电子供体，依普硒靶主要是谷胱甘肽和谷氧还蛋白阴性细菌，一类包括主要病原体。因此，依布硒林和类似化合物可用作抗菌剂，即使对于多抗性菌株也是有用的。以前不知道对ebselen，结核分枝杆菌（结核分枝杆菌）和幽门螺杆菌（胃溃疡和癌症）敏感的两种主要致病菌被证明是优异的靶标。幽门螺杆菌

2. 发明申请

WO2018104777A1 ANTIBIOTIC COMPOSITIONS COMPRISING SILVER AND SELENIUM 审中-公开
公开(公告)号：WO2018104777A1
公开(公告)日：2018-06-14
申请号：PCT/IB2017/001615
申请日：2017-12-05
申请人： HOLMGREN, Arne
发明人： HOLMGREN, Arne , LU, Jun , ZOU, Lili
IPC分类号： A61K33/04 , A61K33/38 , A61P31/04 , A61P31/02
摘要： Disclosed herein are antibiotic compositions, for example compositions that comprise a metal- containing agent and an organoselenium agent, and uses thereof.

3. 发明申请

WO2007137255A3 BACTERIAL THIOREDOXIN REDUCTASE INHIBITORS AND METHODS FOR USE THEREOF 审中-公开
公开(公告)号：WO2007137255A3
公开(公告)日：2007-11-29
申请号：PCT/US2007/069455
申请日：2007-05-22
申请人： THIOREDOXIN SYSTEMS AB , THYOGEN PHARMACEUTICALS, INC. , HOLMGREN, Arne , LU, Jun , VLAMIS-GARDIKAS, Alexios , ZHAO, Rong , KANDASAMY, K. , ENGMAN, Lars , ENGSTRAND, Lars , HOFFNER, Sven
发明人： HOLMGREN, Arne , LU, Jun , VLAMIS-GARDIKAS, Alexios , ZHAO, Rong , KANDASAMY, K. , ENGMAN, Lars , ENGSTRAND, Lars , HOFFNER, Sven
IPC分类号： A61K31/555 , A61K31/385 , A61K31/38
摘要： The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E.coli TrxR with K i of 0.14 µM and 0.46 µM, respectively. E.coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains. Two major pathogenic bacteria, which previously had not been known to be sensitive to ebselen, Mycobacterium tuberculosis (tuberculosis) and Helicobacter pylori (stomach ulcer and cancer), were shown to be excellent targets. Helicobacter pylori was also sensitive to ebsulfur.

4. 发明申请

WO0112657A3 Methods and means for selenoprotein expression 审中-公开
标题翻译：硒蛋白表达的方法和手段
公开(公告)号：WO0112657A3
公开(公告)日：2001-08-23
申请号：PCT/EP0007216
申请日：2000-07-27
申请人： KAROLINSKA INNOVATIONS AB , ARNER ELIAS SET JENO , BOCK AUGUST , HOLMGREN ARNE
发明人： ARNER ELIAS SET JENO , BOCK AUGUST , HOLMGREN ARNE
IPC分类号： C07K14/47 , C12N15/10 , C12N15/12 , C12N15/63 , C12N15/70
CPC分类号： C07K14/47
摘要： In bacterial host cells a mammalian or other heterologous selenoprotein is produced by recombinant expression, employing nucleic acid which comprises a coding sequence for the selenoprotein, a bacterial selenocysteine insertion sequence (SECIS) for insertion of selenocysteine into the protein on production of the protein by expression from the nucleic acid in bacterial host cells and regulatory sequences for expression of the encoded selenoprotein in bacterial host cells. The host cells are preferably cultured under conditions for over-expression of selA, selB, and selC so that the selenoprotein is produced.

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