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1. 发明申请

US20130260405A1 FLUORESCENCE MEASUREMENT METHOD AND FLUORESCENCE MEASUREMENT DEVICE 有权
标题翻译：荧光测量方法和荧光测量装置
公开(公告)号：US20130260405A1
公开(公告)日：2013-10-03
申请号：US13825572
申请日：2011-09-28
申请人： Norikazu Nishino , Mitsuhiro Fukamachi , Fumio Obayashi
发明人： Norikazu Nishino , Mitsuhiro Fukamachi , Fumio Obayashi
IPC分类号： G01N21/64
CPC分类号： G01N21/6486 , G01N21/0303 , G01N21/645 , G01N2021/0367
摘要： In order to provide a fluorescence measurement method and a fluorescence measurement device that are provided by a simpler structure, and are more inexpensive and capable of measuring an amount of fluorescence using a very small amount of sample, using a fluorescence measurement device including a light-blocking measurement box to which a microtube is loaded; a container support part disposed inside the measurement box, the container support part vertically supporting the microtube; an excitation light source part disposed inside the measurement box, the excitation light source part including a light source that horizontally irradiates excitation light a sidewall surface of the loaded microtube; and a fluorescence detection part provided at an upper portion of the measurement box and above the loaded microtube, the fluorescence detection part measuring an amount of fluorescence in a particular wavelength range from a target sample, a microtube charged with a target liquid sample is loaded into the measurement box, the microtube that is uncapped is irradiated laterally in a horizontal direction with excitation light having a particular peak wavelength, and an amount of fluorescence from the target liquid sample excited by light distributed to the entire region of the target liquid inside the tube using a sidewall surface of the microtube as an excitation light waveguide and light leaking from the sidewall surface is measured by a fluorescence detection part for a particular wavelength range.
摘要翻译：为了提供一种通过更简单的结构提供的荧光测量方法和荧光测量装置，并且更便宜并且能够使用非常少量的样品来测量荧光量，使用包括发光元件的荧光测量装置，加载微管的阻塞测量盒; 设置在测量箱内部的容器支撑部分，容器支撑部分垂直地支撑微管; 激发光源部，其设置在测量箱的内部，所述激发光源部包括将激发光水平地照射到所述负载的微管的侧壁面的光源; 以及荧光检测部，其设置在测定盒的上部并且在载置的微管的上方，荧光检测部将从目标样品，装有目标液体样品的微管中的荧光量测定到特定的波长范围内，测量盒，未加盖的微管在水平方向上用具有特定峰值波长的激发光照射，并且来自被光激发的目标液体样品的荧光量分布在管内的目标液体的整个区域使用微管的侧壁表面作为激发光波导，并且通过用于特定波长范围的荧光检测部分测量从侧壁表面泄漏的光。

2. 发明申请

US20090023200A1 PARTICLE FOR DETECTING ENZYME ACTIVITY, METHOD FOR DETECTING THE ENZYME ACTIVITY AND ENZYME ACTIVITY DETECTION DEVICE BY THE USE THEREOF 审中-公开
标题翻译：用于检测酶活性的颗粒，用于检测酶活性的方法及其使用的酶活性检测装置
公开(公告)号：US20090023200A1
公开(公告)日：2009-01-22
申请号：US11813543
申请日：2005-10-25
申请人： Norikazu Nishino , Tamaki Kato
发明人： Norikazu Nishino , Tamaki Kato
IPC分类号： G01N33/53 , C12M1/34
CPC分类号： G01N21/6428 , C12Q1/37 , G01N33/582 , G01N33/585 , G01N2500/00
摘要： An object is to provide a particle for detecting an enzyme activity wherein by measuring an intensity of a fluorescence wavelength in a sample solution, it is possible to not only detect the presence or absence of an enzyme but also accurately perform a quantitative analysis of the enzyme in the sample solution, handleability is excellent as well as measurement accuracy and quantitative property can be enhanced because the present invention is hardly influenced by absorbed moisture and weighing errors hardly occur, and further productivity is remarkably excellent because complicated steps such as a step of cleaving and purifying a synthesized peptide and a step of lyophilizing are not required upon production thereof.The particle 1 for detecting the enzyme activity of the present invention comprises a particle 2 and a first compound 3 binding the particle 2 to one end, binding a first fluorescent group 4 to the other end and having a cleavage site by an enzyme 5 in a sample solution.
摘要翻译：目的是提供用于检测酶活性的粒子，其中通过测量样品溶液中的荧光波长的强度，可以不仅检测酶的存在或不存在，而且可以精确地进行酶的定量分析在样品溶液中，可操作性优异且测量精度高，定量性能可以提高，因为本发明几乎不受吸收水分的影响，难以发生称重误差，进一步提高生产率，因为复杂的步骤如裂解步骤并且纯化合成的肽，并且在制备时不需要冷冻干燥步骤。用于检测本发明的酶活性的颗粒1包含颗粒2和将颗粒2结合到一端的第一化合物3，将第一荧光基团4与另一端结合并在酶5中具有切割位点样品溶液。

3. 发明申请

US20050277583A1 Histone deacetylase inhibitors and process for producing the same 失效
标题翻译：组蛋白脱乙酰酶抑制剂及其制备方法
公开(公告)号：US20050277583A1
公开(公告)日：2005-12-15
申请号：US10505380
申请日：2003-02-20
申请人： Minoru Yoshida , Norikazu Nishino , Saeharu Horinouchi
发明人： Minoru Yoshida , Norikazu Nishino , Saeharu Horinouchi
IPC分类号： A61K38/00 , A61P17/00 , A61P31/00 , A61P35/00 , A61P37/00 , A61P43/00 , C07K5/12 , A61K38/12
CPC分类号： C07K5/126 , A61K38/00
摘要： Compounds represented by formula (1) have strong inhibitory activity that is selective towards HDAC1 and HDAC4. Therefore, the compounds of the present invention are useful as pharmaceutical agents for treating or preventing diseases caused by HDAC1 and HDAC4.
摘要翻译：由式（1）表示的化合物具有对HDAC1和HDAC4具有选择性的强抑制活性。因此，本发明的化合物可用作治疗或预防HDAC1和HDAC4引起的疾病的药剂。

4. 发明授权

US08158587B2 Compound having histone deacetylase-inhibiting activity, and pharmaceutical composition comprising the compound as an active ingredient 有权
标题翻译：具有组蛋白脱乙酰酶抑制活性的化合物和包含该化合物作为活性成分的药物组合物
公开(公告)号：US08158587B2
公开(公告)日：2012-04-17
申请号：US12440180
申请日：2007-07-30
申请人： Norikazu Nishino , Minoru Yoshida , Junichi Nakagawa
发明人： Norikazu Nishino , Minoru Yoshida , Junichi Nakagawa
IPC分类号： A61K38/12
CPC分类号： C07K5/126 , A61K38/00
摘要： A novel compound having histone deacetylase-inhibiting activity which is a cyclic tetrapeptide derivative represented by the general formula (1) given below and a pharmaceutical composition comprising such compound as an active ingredient. (In the formula, the cyclic tetrapeptide moiety has a known structure; R1 and R2 each independently represents an alkylene group containing 1 to 6 carbon atoms, which may be branched; X represents a group or bond selected from among —CO—, —O—, —S— or —SO—; Y represents a hydrogen or halogen atom, a phenyl group (including a substituted form), a pyridyl group (including a substituted form), an alkyl group (including a halogen-substituted form; hereinafter the same shall apply) containing 1 to 6 carbon atoms, an alkyloxy group containing 1 to 6 carbon atoms, an alkylcarbonyl group containing 1 to 6 carbon atoms, an alkyloxycarbonyl group containing 1 to 6 carbon atoms, an alkylthio group containing 1 to 6 carbon atoms, an alkylthiocarbonyl group containing 1 to 6 carbon atoms or a mono- or dialkylamino group containing 1 to 6 carbon atoms; when Y is a phenyl group (including a substituted form) or a pyridyl group (including a substituted form), it may form a further cyclic structure bound to R2.)
摘要翻译：具有组蛋白脱乙酰酶抑制活性的新化合物，其为下述通式（1）表示的环状四肽衍生物，以及含有作为活性成分的化合物的药物组合物。（式中，环状四肽部分具有已知的结构; R 1和R 2各自独立地表示可以是支链的含有1〜6个碳原子的亚烷基; X表示选自-CO - ， - O - ， - S-或-SO-; Y表示氢或卤原子，苯基（包括取代基），吡啶基（包括取代基），烷基（包括卤素取代基同样适用）含有1至6个碳原子，含有1至6个碳原子的烷氧基，含有1至6个碳原子的烷基羰基，含有1至6个碳原子的烷氧基羰基，含1至6个碳原子的烷硫基原子，含有1〜6个碳原子的烷硫基羰基或含有1〜6个碳原子的单或二烷基氨基;当Y为苯基（包括取代基）或吡啶基（包括取代基）时，形成进一步的循环 c结构绑定到R2。）

5. 发明授权

US07662778B2 Histone deacetylase inhibitor and process for producing the same 失效
标题翻译：组蛋白脱乙酰酶抑制剂及其制备方法
公开(公告)号：US07662778B2
公开(公告)日：2010-02-16
申请号：US10561298
申请日：2004-06-18
申请人： Minoru Yoshida , Norikazu Nishino
发明人： Minoru Yoshida , Norikazu Nishino
IPC分类号： A61K38/00
CPC分类号： C07K5/126
摘要： HDAC inhibitor of the general formula (1) exhibits strong inhibitory activity against various subtype HDACs. The compound is useful as a medicinal agent for the treatment or prevention of HDAC 1, 4 and 6-related diseases. There is further provided a process for producing the compound which is capable of readily synthesizing various types of compounds and is promising in the contribution to the development of HDAC inhibitor having novel properties, etc.
摘要翻译：通式（1）的HDAC抑制剂对各种亚型HDAC具有强烈的抑制活性。该化合物可用作治疗或预防HDAC 1,4和6相关疾病的药物。进一步提供一种能够容易地合成各种化合物并且有助于对具有新性能的HDAC抑制剂的发展的贡献的化合物的制备方法等。

6. 发明授权

US07488712B2 Histone deacetylase inhibitors and methods for producing the same 失效
标题翻译：组蛋白脱乙酰酶抑制剂及其制备方法
公开(公告)号：US07488712B2
公开(公告)日：2009-02-10
申请号：US10505380
申请日：2003-02-20
申请人： Minoru Yoshida , Norikazu Nishino , Sueharu Horinouchi
发明人： Minoru Yoshida , Norikazu Nishino , Sueharu Horinouchi
IPC分类号： A61K38/00
CPC分类号： C07K5/126 , A61K38/00
摘要： Compounds represented by formula (1) have strong inhibitory activity that is selective towards HDAC1 and HDAC4. Therefore, the compounds of the present invention are useful as pharmaceutical agents for treating or preventing diseases caused by HDAC1 and HDAC4.
摘要翻译：由式（1）表示的化合物具有对HDAC1和HDAC4具有选择性的强抑制活性。因此，本发明的化合物可用作治疗或预防HDAC1和HDAC4引起的疾病的药剂。

7. 发明授权

US08848188B2 Fluorescence measurement method and fluorescence measurement device 有权
标题翻译：荧光测量方法和荧光测量装置
公开(公告)号：US08848188B2
公开(公告)日：2014-09-30
申请号：US13825572
申请日：2011-09-28
申请人： Norikazu Nishino , Mitsuhiro Fukamachi , Fumio Obayashi
发明人： Norikazu Nishino , Mitsuhiro Fukamachi , Fumio Obayashi
IPC分类号： G01N21/00 , G01N21/64 , G01N21/03
CPC分类号： G01N21/6486 , G01N21/0303 , G01N21/645 , G01N2021/0367
摘要： In order to provide a fluorescence measurement method and a fluorescence measurement device that are provided by a simpler structure, and are more inexpensive and capable of measuring an amount of fluorescence using a very small amount of sample, using a fluorescence measurement device including a light-blocking measurement box to which a microtube is loaded; a container support part disposed inside the measurement box, the container support part vertically supporting the microtube; an excitation light source part disposed inside the measurement box, the excitation light source part including a light source that horizontally irradiates excitation light a sidewall surface of the loaded microtube; and a fluorescence detection part provided at an upper portion of the measurement box and above the loaded microtube, the fluorescence detection part measuring an amount of fluorescence in a particular wavelength range from a target sample, a microtube charged with a target liquid sample is loaded into the measurement box, the microtube that is uncapped is irradiated laterally in a horizontal direction with excitation light having a particular peak wavelength, and an amount of fluorescence from the target liquid sample excited by light distributed to the entire region of the target liquid inside the tube using a sidewall surface of the microtube as an excitation light waveguide and light leaking from the sidewall surface is measured by a fluorescence detection part for a particular wavelength range.
摘要翻译：为了提供一种通过更简单的结构提供的荧光测量方法和荧光测量装置，并且更便宜并且能够使用非常少量的样品来测量荧光量，使用包括发光元件的荧光测量装置，加载微管的阻塞测量盒; 设置在测量箱内部的容器支撑部分，容器支撑部分垂直地支撑微管; 激发光源部，其设置在测量箱的内部，所述激发光源部包括将激发光水平地照射到所述负载的微管的侧壁面的光源; 以及荧光检测部，其设置在测定盒的上部并且在负载的微管的上方，荧光检测部分测量来自目标样品的特定波长范围内的荧光量，将装有目标液体样品的微管加载到测量盒，未加盖的微管在水平方向上用具有特定峰值波长的激发光照射，并且来自被光激发的目标液体样品的荧光量分布在管内的目标液体的整个区域使用微管的侧壁表面作为激发光波导，并且通过用于特定波长范围的荧光检测部分测量从侧壁表面泄漏的光。

8. 发明申请

US20130029878A1 Method for Assaying Histone Methylation Enzyme Activity 有权
标题翻译：分析组蛋白甲基化酶活性的方法
公开(公告)号：US20130029878A1
公开(公告)日：2013-01-31
申请号：US13639334
申请日：2011-04-15
申请人： Norikazu Nishino , Yasushi Takemoto , Akihiro Ito , Minoru Yoshida
发明人： Norikazu Nishino , Yasushi Takemoto , Akihiro Ito , Minoru Yoshida
IPC分类号： G01N21/64 , C40B30/08 , C07K2/00 , G01N21/78
CPC分类号： C12Q1/37 , C07D311/18 , C07D311/82 , C07D473/32 , C12Q1/48 , G01N33/6875 , G01N2500/00 , Y02P20/55
摘要： Provided are a method for measuring histone methyltransferase activity, a method for screening for compounds that inhibit histone methyltransferase activity, a reagent kit for measuring histone methyltransferase activity, and a kit for screening for compounds that inhibit histone methyltransferase activity. A substrate compound represented by general formula (I): R1—X—K—R2 (I), or a salt thereof, wherein R1 represents a hydrogen atom or a protecting group for an amino terminus; X represents a peptide consisting of 0 or 1 or more amino acid residues; K represents a lysine residue; and R2 represents a dye label linked via an amide bond to the carbonyl terminus of a lysine residue, wherein the cleavage of the amide bond by peptidase changes the fluorescence property or chromogenic property of the dye label, and the methylation of the ε amino group of the lysine residue by the histone methyltransferase decreases susceptibility to peptidase, is used.
摘要翻译：提供了测定组蛋白甲基转移酶活性的方法，用于筛选抑制组蛋白甲基转移酶活性的化合物的方法，用于测定组蛋白甲基转移酶活性的试剂盒和用于筛选抑制组蛋白甲基转移酶活性的化合物的试剂盒。由通式（I）表示的底物化合物：R1-X-K-R2（I）或其盐，其中R1表示氢原子或氨基末端的保护基; X表示由0或1个或更多个氨基酸残基组成的肽; K表示赖氨酸残基; R2表示通过酰胺键与赖氨酸残基的羰基末端连接的染料标记，其中通过肽酶切割酰胺键改变染料标记的荧光性质或显色性质，以及染料标记的甲基化。使用组蛋白甲基转移酶的赖氨酸残基的氨基降低对肽酶的易感性。

9. 发明申请

US20070185071A1 Histone deacetylase inhibitor and process for producing the same 失效
标题翻译：组蛋白脱乙酰酶抑制剂及其制备方法
公开(公告)号：US20070185071A1
公开(公告)日：2007-08-09
申请号：US10561298
申请日：2004-06-18
申请人： Minoru Yoshida , Norikazu Nishino
发明人： Minoru Yoshida , Norikazu Nishino
IPC分类号： A61K31/555
CPC分类号： C07K5/126
摘要： HDAC inhibitors represented by formula (1) show strong inhibitory activity against various subtypes of HDACs. The compounds of the present invention find utility as pharmaceutical agents for treating or preventing diseases associated with HDAC 1, 4, and 6. The methods for producing the compounds of the present invention enable easy and simple synthesis of various types of these compounds, and are expected to contribute to the development of HDAC inhibitors having novel properties and the like.
摘要翻译：由式（1）表示的HDAC抑制剂显示出对各种HDACs亚型的强抑制活性。本发明的化合物可用作治疗或预防与HDAC 1,4和6有关的疾病的药物。本发明化合物的制备方法能容易和简单地合成各种类型的这些化合物，并且是预期有助于开发具有新颖性质等的HDAC抑制剂。

10. 发明授权

US06399568B1 Cyclic tetrapeptide derivatives and medicinal use thereof 失效
标题翻译：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。

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