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    SRM/MRM Assay for the 6-O-methylguanine-DNA methyltransferase (MGMT) protein
    7.
    发明申请
    SRM/MRM Assay for the 6-O-methylguanine-DNA methyltransferase (MGMT) protein 审中-公开
    6-O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）蛋白的SRM / MRM测定

    公开(公告)号：US20160334408A1

    公开(公告)日：2016-11-17

    申请号：US15156289

    申请日：2016-05-16

    申请人： Expression Pathology, Inc.

    发明人： David B. KRIZMAN ,  Todd Hembrough ,  Eunkyung An ,  Sheeno Thyparambil ,  Wei-Li Lao

    IPC分类号： G01N33/574

    CPC分类号： G01N33/57496 ,  C12Q1/48 ,  C12Y201/01063 ,  G01N2333/91017 ,  G01N2560/00

    摘要： The current disclosure provides methods for detecting and quantitating the 6-O-methylguanine-DNA methyltransferase protein (MGMT) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed with formaldehyde containing agents/fixatives and may include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and/or paraffin embedded. A protein sample is prepared from the biological sample and the MGMT protein is quantitated in the sample using SRM/MRM mass spectrometry by quantitating one or more fragment peptides.

    摘要翻译： 目前的公开内容提供了通过选择反应监测/多反应监测（SRM / MRM）质谱法的方法，在已经在福尔马林中固定的生物样品中直接检测和定量6-O-甲基鸟嘌呤-DNA甲基转移酶蛋白（MGMT）的方法 。 这样的生物样品被化学保存并用含甲醛的固定剂固定，并且可以包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋（FFPE）组织/细胞，FFPE组织块和来自那些块的细胞，以及组织培养细胞 已被固定和/或石蜡包埋。 从生物样品制备蛋白质样品，并通过定量一个或多个片段肽，使用SRM / MRM质谱法在样品中定量MGMT蛋白质。

    A BACTERIAL SURROGATE FOR TESTING OF ANTIMALARIALS: THYA KNOCKOUT, FOLA KNOCKOUT, FOLP KNOCKOUT, AND FOLK KNOCKOUT BACTERIA FOR TESTING OF INHIBITION OF ANTIFOLATE PATHWAY
    8.
    发明申请
    A BACTERIAL SURROGATE FOR TESTING OF ANTIMALARIALS: THYA KNOCKOUT, FOLA KNOCKOUT, FOLP KNOCKOUT, AND FOLK KNOCKOUT BACTERIA FOR TESTING OF INHIBITION OF ANTIFOLATE PATHWAY 有权
    用于测试抗菌药物的细菌物质：THYA KNOCKOUT，FOLA KNOCKOUT，FOLP KNOCKOUT和FOLK KNOCKOUT BACTERIA用于测试抗静电途径

    公开(公告)号：US20160230178A1

    公开(公告)日：2016-08-11

    申请号：US15025881

    申请日：2014-09-18

    申请人： NATIONAL SCIENCE AND TECHNOLOGY DEVELOPMENT AGENCY

    发明人： Nattida SUWANAKITTI ,  Yuwadee TALAWANICH ,  Yongyuth YUTHAVONG ,  Sumalee KAMCHONWONGPAISAN

    IPC分类号： C12N15/70 ,  C12Q1/48

    CPC分类号： C12N15/70 ,  C12N9/003 ,  C12N9/1007 ,  C12N9/1085 ,  C12N9/1235 ,  C12N9/93 ,  C12Q1/48 ,  G01N2333/91017 ,  G01N2333/91165 ,  G01N2333/91171

    摘要： In this invention, cell lines are created for enzyme inhibitory testing of inhibitors against Plasmodium falciparum DHFR-TS and HPPK-DHPS. Provided the complementing DHFR-TS and HPPK-DHPS have sufficient activities to support growth of the surrogates in un-supplemented medium, the same surrogates could be used for screening inhibitors of targets against other parasite and pathogen species e.g. Plasmodium vivax, Trypanosoma brucei, Trypanosoma cruzi, Toxoplasma gondii or Mycobacterium tuberculosis. The cell lines in this invention are Escherichia coli strain whose thyA, folA, folK, and folP genes were disrupted using genetic knockout coupled with elimination of antibiotic resistance markers. The thyA KO, folP KO, folK KO, thyAfolA KO, folKfolP KO, thyAfolAfolP KO, thyAfolAfolK KO and thyAfolAfolKfolP KO E. coli cell lines are easy and convenient for testing single and combination drugs as plasmids bearing complementing parasite genes can be introduced simply by transformation using standard antibiotic selection.

    摘要翻译： 在本发明中，产生了针对恶性疟原虫DHFR-TS和HPPK-DHPS的抑制剂进行酶抑制测试的细胞系。 如果补充DHFR-TS和HPPK-DHPS具有足够的活性来支持未补充培养基中替代物的生长，则相同的替代物可用于筛选针对其他寄生虫和病原体物种的靶标的抑制剂，例如 间日疟原虫，布鲁斯锥虫，克氏锥虫，弓形虫或结核分枝杆菌。 本发明中的细胞系是大肠杆菌菌株，其thyA，folA，folk和folP基因使用遗传敲除与消除抗生素抗性标记相结合而被破坏。 thy A O，K K，，，，，by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by by 使用标准抗生素选择进行转化。

    DOT1L PROBES
    9.
    发明申请
    DOT1L PROBES 有权

    公开(公告)号：US20160146817A1

    公开(公告)日：2016-05-26

    申请号：US14904572

    申请日：2014-07-28

    申请人： DANA-FARBER CANCER INSTITUTE, INC.

    发明人： James E. Bradner ,  Alexander Federation ,  Jun Qi

    IPC分类号： G01N33/573 ,  C07H19/16 ,  G01N33/58

    CPC分类号： G01N33/573 ,  A61K31/7076 ,  C07H19/16 ,  G01N33/582 ,  G01N2333/91017 ,  G01N2500/02

    摘要： The present invention relates to compound that bind Histone H3-lysine79 (H3K79) methyl transferase (DOTIL). The disclosed compounds are useful as for assessing the activity of DOTIL and for identifying inhibitors of DOTIL. Described herein are probes useful for both assessing the activity of DOTIL and identifying inhibitors of DOTIL. These probes can be used in various assays, including Amplified Luminescent Proximity Homogeneous Assays (“ALPHA” assays), Differential Scanning Fluorimetry (DFS) Assay, and Fluorescence Polarization (FP) assays used for high-throughput screening (HTS) for small molecule drug discovery. The compounds can also be used as a pull down agent for target identification.

    摘要翻译： 本发明涉及结合组蛋白H3-赖氨酸79（H3K79）甲基转移酶（DOTIL）的化合物。 所公开的化合物可用于评估DOTIL的活性和用于鉴定DOTIL的抑制剂。 本文描述的是可用于评估DOTIL的活性和鉴定DOTIL抑制剂的探针。 这些探针可用于各种测定，包括用于小分子药物的高通量筛选（HTS）的扩增发光近似均质测定（“ALPHA”测定），差示扫描荧光测定（DFS）测定和荧光偏振（FP）测定） 发现。 这些化合物也可以用作目标识别的下拉剂。