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    Cyclic tetrapeptide derivatives and medicinal use thereof
    1.
    发明授权
    Cyclic tetrapeptide derivatives and medicinal use thereof 失效
    环状四肽衍生物及其医药用途

    公开(公告)号：US06399568B1

    公开(公告)日：2002-06-04

    申请号：US09486783

    申请日：2000-03-01

    申请人： Norikazu Nishino ,  Minoru Yoshida ,  Sueharu Horinouchi ,  Yasuhiko Komatsu ,  Tsutomu Mimoto

    发明人： Norikazu Nishino ,  Minoru Yoshida ,  Sueharu Horinouchi ,  Yasuhiko Komatsu ,  Tsutomu Mimoto

    IPC分类号： A61K3812

    CPC分类号： C07K5/126 ,  A61K38/00

    摘要： A cyclic tetrapeptide derivative represented by the general formula (I): wherein: R11, R12, R21 and R22 independently denote a monovalent group selected from hydrogen, a linear or branched alkyl group with 6 or less carbon atoms, benzyl group, 4-methoxybenzyl group, 3-indolylmethyl group, (N-methoxy-3-indolyl) methyl group, (N-formyl-3-indolyl)methyl group, etc.; R3 denotes a divalent group selected from a linear chained hydrocarbon group with 3 or 4 carbon atoms, or the linear branched hydrocarbon group having a branched chain added to the chain, or a divalent group substituted with a heteroatom; R4 denotes a divalent chained hydrocarbon group with 4 to 6 carbon atoms, or a divalent group derived from said hydrocarbon group by addition etc. of a branched chain on said chain; and a pharmaceutically acceptable salt thereof, or an analogous cyclic tetrapeptide derivative compound; as well as a histone deacetylase enzyme inhibitor, an MHC class-I molecule expression promoting agent and a pharmaceutical composition that comprise said cyclic tetrapeptide derivative as an effective ingredient.

    摘要翻译： 由通式（I）表示的环状四肽衍生物：其中：R11，R12，R21和R22独立地表示选自氢，碳原子数6以下的直链或支链烷基，苄基，4-甲氧基苄基 （3-甲氧基-3-吲哚基）甲基，（N-甲酰基-3-吲哚基）甲基等。 R3表示选自具有3或4个碳原子的直链状烃基或者在该链上添加有支链的直链支链烃基或被杂原子取代的二价基团的二价基团; R4表示二价链状烃基 或含有4〜6个碳原子的二价基团，或通过所述链上的支链的加成等衍生自所述烃基的二价基团; 和其药学上可接受的盐，或类似的环状四肽衍生物化合物; 以及组蛋白脱乙酰酶酶抑制剂，MHC class I分子表达促进剂和包含所述环状四肽衍生物作为有效成分的药物组合物。

    Cyclic tetrapeptide derivatives and pharmaceutical uses thereof
    2.
    发明授权
    Cyclic tetrapeptide derivatives and pharmaceutical uses thereof 失效
    环状四肽衍生物及其药物用途

    公开(公告)号：US06825317B2

    公开(公告)日：2004-11-30

    申请号：US09945237

    申请日：2001-08-31

    申请人： Norikazu Nishino ,  Minoru Yoshida ,  Sueharu Horinouchi ,  Yasuhiko Komatsu

    发明人： Norikazu Nishino ,  Minoru Yoshida ,  Sueharu Horinouchi ,  Yasuhiko Komatsu

    IPC分类号： C07K752

    CPC分类号： C07K5/126 ,  A61K38/00

    摘要： The present invention provides a cyclic tetrapeptide derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: wherein each of R21 and R22 independently denotes hydrogen, a linear C1-C6-alkyl group to which a non-aromatic cycloalkyl group or an optionally substituted aromatic ring may be attached, or a branched C3-C6-alkyl group to which a non-aromatic cycloalkyl group or an optionally substituted aromatic ring may be attached; and each of R1 and R3 independently denotes a linear C1-C5-alkylene group which may have a C1-C6 side chain, in which the side chain may form a condensed ring structure on the alkylene chain. The present invention also provides a histone deacetylase inhibitor, an MHC class-I molecule expression-promoting agent and a pharmaceutical composition, each of which comprises the above cyclic tetrapeptide derivative or pharmaceutically acceptable salt thereof as an active ingredient.

    摘要翻译： 本发明提供由以下通式（I）表示的环状四肽衍生物或其药学上可接受的盐：R21和R22独立地表示氢，非芳香族环烷基的直链C 1 -C 6 - 烷基或 可以连接任选取代的芳环，或者可以连接非芳族环烷基或任选取代的芳环的支链C 3 -C 6 - 烷基; R 1和R 3的每一个独立地表示可以具有C 1 -C 6侧链的直链C 1 -C 5亚烷基，其中侧链可以在亚烷基链上形成稠环结构。本发明还提供组蛋白脱乙酰酶抑制剂 ，MHC I类分子表达促进剂和药物组合物，其各自包含上述环状四肽衍生物或其药学上可接受的盐作为活性成分。

    Reduced FK228 and use thereof
    4.
    发明授权
    Reduced FK228 and use thereof 有权
    减少FK228及其使用

    公开(公告)号：US07056884B2

    公开(公告)日：2006-06-06

    申请号：US10333063

    申请日：2001-07-09

    申请人： Hidenori Nakajima ,  Akito Tanaka ,  Minoru Yoshida ,  Sueharu Horinouchi

    发明人： Hidenori Nakajima ,  Akito Tanaka ,  Minoru Yoshida ,  Sueharu Horinouchi

    IPC分类号： A61K38/00 ,  C07K16/00

    CPC分类号： C07K11/02 ,  A61K38/00 ,  C07K5/101 ,  Y02P20/55

    摘要： The present invention relates to reduced FK228 of the formula (I) wherein R1 and R2 are the same or different and each is a hydrogen atom or a thiol-protecting group, or a salt thereof, and a histone deacetylase inhibitor containing this compound, an expression potentiator and a reactivation promoter of a transgene, and pharmaceutical agents containing them as active ingredients. The reduced FK228 or a salt thereof has a strong histone deacetylase inhibitory activity and this compound can be used for the prophylaxis or treatment of various diseases, in which histone deacetylation is involved, and for the gene therapy of such diseases.

    摘要翻译： 本发明涉及式（I）的还原型FK228，其中R 1和R 2相同或不同，各自为氢原子或硫醇保护基 或其盐，以及含有该化合物的组蛋白脱乙酰酶抑制剂，转基因的表达增强子和再活化启动子以及含有它们作为有效成分的药剂。 还原的FK228或其盐具有强的组蛋白脱乙酰酶抑制活性，该化合物可用于预防或治疗涉及组蛋白脱乙酰化的各种疾病和用于这些疾病的基因治疗。

    Human CRM1 Protein
    5.
    发明授权
    Human CRM1 Protein 失效
    人类CRM1蛋白

    公开(公告)号：US5948883A

    公开(公告)日：1999-09-07

    申请号：US975527

    申请日：1997-11-20

    申请人： Minoru Yoshida ,  Sueharu Horinouchi ,  Kazunori Nishi

    发明人： Minoru Yoshida ,  Sueharu Horinouchi ,  Kazunori Nishi

    IPC分类号： A61K38/00 ,  C07K14/47 ,  C12N15/12

    CPC分类号： C07K14/4703 ,  A61K38/00

    摘要： A protein which comprises the sane or substantially the same amino acid sequence as that represented by SEQ ID NO:1, its partial peptide and their salts are disclosed. DNA encoding the protein or its partial peptide is also disclosed. The protein, its partial peptide or a salt thereof is an inhibitory factor of a transcription factor and, therefore, it is useful as medicine such as prophylactic and therapeutic drugs of, for example, tumors. The DNA is useful as a gene diagnosing drug. The antibody against the protein, etc. is also disclosed. The antibody is used for, for example, quantitative determination of the protein, etc. in a specimen fluid. The protein, etc. are also useful as a reagent for screening for compounds or their salts which promote the function of the protein, etc.

    摘要翻译： 公开了包含与SEQ ID NO：1所示的基本相同的氨基酸序列的蛋白质，其部分肽及其盐。 还公开了编码蛋白质或其部分肽的DNA。 蛋白质，其部分肽或其盐是转录因子的抑制因子，因此可用作例如肿瘤的预防和治疗药物等药物。 该DNA可用作诊断药物的基因。 还公开了针对蛋白质等的抗体。 抗体用于例如样品流体中蛋白质等的定量测定。 蛋白质等也可用作筛选促进蛋白质等功能的化合物或其盐的试剂。

    DNA encoding polypeptide having nitrile hydratase activity and method for producing amides from nitriles with transformant containing the same
    7.
    发明授权
    DNA encoding polypeptide having nitrile hydratase activity and method for producing amides from nitriles with transformant containing the same 失效
    具有NITRILE HYDRATASE活性的DNA编码多肽和从含有其的转化体的NITRILES生产氨基的方法

    公开(公告)号：US5130235A

    公开(公告)日：1992-07-14

    申请号：US372449

    申请日：1989-06-28

    申请人： Teruhiko Beppu ,  Sueharu Horinouchi ,  Osamu Ikehata ,  Takakazu Endo

    发明人： Teruhiko Beppu ,  Sueharu Horinouchi ,  Osamu Ikehata ,  Takakazu Endo

    IPC分类号： C12N1/21 ,  C12N9/78 ,  C12N9/88 ,  C12N15/09 ,  C12N15/55 ,  C12P13/02 ,  C12R1/15 ,  C12R1/19

    CPC分类号： C12P13/02 ,  C12N9/78

    摘要： A DNA which encodes polypeptide carrying two specific amino acid sequences and having nitrile hydratase activity; a method for producing nitrile hydratase by incubating a transformant made by the transformation with a recombinant DNA prepared by integrating the foregoing DNA into a vector in a medium and harvesting nitrile hydratase accumulated in the medium; and a method for producing amides by incubating the foregoing transformant and then converting nitriles into corresponding amides by the action of the obtained nitrile hydratase or by making a culture solution, isolates, treated cells or their immobilized products act upon nitriles to produce corresponding amides.

    摘要翻译： 编码携带两个特定氨基酸序列并具有腈水合酶活性的多肽的DNA; 通过将通过转化制备的转化体与通过将上述DNA整合到培养基中的载体并收获在培养基中积累的腈水合酶而制备的重组DNA来生产腈水合酶的方法; 以及通过温育上述转化体然后通过所得腈水合酶的作用将腈转化为相应的酰胺或通过使培养液，分离物，经处理的细胞或其固定化产物作用于腈以产生相应的酰胺的方法来生产酰胺。