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1. 发明申请

US20070105796A1 Method for inhibiting telomerase activity and inhibitor thereof 审中-公开
标题翻译：抑制端粒酶活性的方法及其抑制剂
公开(公告)号：US20070105796A1
公开(公告)日：2007-05-10
申请号：US10563074
申请日：2005-04-28
申请人： Naoya Wada , Takashi Okamoto , Keiji Tanigaki , Hirofumi Doi , Yasuhiro Kikuchi , Kensaku Imai
发明人： Naoya Wada , Takashi Okamoto , Keiji Tanigaki , Hirofumi Doi , Yasuhiro Kikuchi , Kensaku Imai
IPC分类号： A61K48/00
CPC分类号： C12N9/1205
摘要： The present invention provides a method for inhibiting the activation of telomerase and an agent for inhibiting the activation of telomerase, a method for inhibiting telomerase activity and an agent for inhibiting telomerase activity, a method for preventing and/or a method for treating a cancer disease, an agent for preventing and/or an agent for treating a cancer disease, all of which comprises inhibiting the binding of MAPKAPK3 to TERT that is a catalytic subunit of telomerase or inhibiting the phosphorylation of TERT by active MAPKAPK3; a method of identifying a compound that inhibits the binding of MAPKAPK3 to TERT or a compound that inhibits the phosphorylation of TERT by active MAPKAPK3; and a reagent kit.
摘要翻译：本发明提供抑制端粒酶活化的方法和抑制端粒酶活化的试剂，抑制端粒酶活性的方法和抑制端粒酶活性的方法，预防和/或治疗癌症的方法，用于预防和/或治疗癌症疾病的药物，所有这些都包括抑制MAPKAPK3与作为端粒酶催化亚基的TERT的结合或抑制活性MAPKAPK3的TERT磷酸化; 鉴定抑制MAPKAPK3与TERT结合的化合物或抑制活性MAPKAPK3磷酸化TERT的化合物的方法; 和试剂盒。

2. 发明申请

US20080004355A1 Method for Inhibiting Telomerase Activity and an Agent for Inhibiting the Same 审中-公开
标题翻译：抑制端粒酶活性的方法及其抑制剂
公开(公告)号：US20080004355A1
公开(公告)日：2008-01-03
申请号：US11793959
申请日：2005-12-27
申请人： Naoya Wada , Takashi Okamoto , Keiji Tanigaki , Hirofumi Doi , Kensaku Imai
发明人： Naoya Wada , Takashi Okamoto , Keiji Tanigaki , Hirofumi Doi , Kensaku Imai
IPC分类号： A61K35/00 , A61P35/00 , C12N15/63 , C12N5/00 , C12N9/10 , C12Q1/34 , C12Q1/48 , C12Q1/68
CPC分类号： C12Y207/07049 , A61K45/06 , C12N9/1241 , G01N33/574 , G01N2333/9125 , G01N2333/916 , G01N2500/02
摘要： A method is described for enhancing degradation of telomerase. This method includes inhibiting the binding of TERT (telomerase catalytic subunit) to USP21, the binding of NEDD8-conjugated TERT to USP21, or the NEDD8 deconjugation by USP21 from NEDD8-conjugated TERT. A method of inhibiting telomerase activity is also described. The method includes utilizing the method of enhancing the degradation. A method of identifying a compound that inhibits the binding or the NEDD8 deconjugation is further described. An agent for inhibiting telomerase activity is described. An agent for preventing and/or treating diseases attributable to the enhanced telomerase activity is described and includes an inhibitory agent. Also, a method of preventing and/or treating diseases is described and includes using the inhibition method or the inhibitory agent. Further, a reagent kit is described.
摘要翻译：描述了一种增强端粒酶降解的方法。该方法包括抑制TERT（端粒酶催化亚单位）与USP21的结合，NEDD8缀合的TERT与USP21的结合，或者通过NEDD8缀合的TERT的USP21的NEDD8解缀。还描述了抑制端粒酶活性的方法。该方法包括利用增强降解的方法。进一步描述鉴定抑制结合或NEDD8解缀合的化合物的方法。描述了抑制端粒酶活性的药剂。描述了用于预防和/或治疗归因于增强的端粒酶活性的疾病的药剂，并且包括抑制剂。此外，描述了预防和/或治疗疾病的方法，并且包括使用抑制方法或抑制剂。此外，描述了试剂盒。

3. 发明申请

US20060276387A1 Method of controlling transcription insulin gene 审中-公开
标题翻译：控制转录胰岛素基因的方法
公开(公告)号：US20060276387A1
公开(公告)日：2006-12-07
申请号：US10544061
申请日：2004-11-26
申请人： Hirofumi Doi , Kensaku Imai , Naoya Wada
发明人： Hirofumi Doi , Kensaku Imai , Naoya Wada
IPC分类号： A61K38/22 , C12Q1/68 , G01N33/53
CPC分类号： C07K14/62 , G01N33/74 , G01N2500/02
摘要： A method for promoting insulin gene transcription, which comprises the step of inhibiting binding of IPF1 and any one of proteins selected from the following group: (i) HNF3G, (ii) PHF1, and (iii) DLX4; and a method for screening a substance that promotes insulin gene transcription, which comprises the step of bringing a test substance into contact with IPF1 and/or any one of proteins selected from the following group under a condition that allows the binding of IPF1 and said protein and then determining whether or not the test substance inhibits the binding of IPF1 and said protein by detecting presence or absence, or change of a signal and/or a marker generated by the binding of IPF1 and said protein in a system in which the signal and/or the marker can be detected: (i) HNF3G, (ii) PHF1, and (iii) DLX4.
摘要翻译：一种促进胰岛素基因转录的方法，其包括抑制IPF1与选自以下组中的任何一种蛋白质结合的步骤：（i）HNF3G，（ii）PHF1和（iii）DLX4; 以及用于筛选促进胰岛素基因转录的物质的方法，其包括在允许IPF1和所述蛋白质结合的条件下使测试物质与IPF1和/或选自以下组的任何一种蛋白质接触的步骤然后通过检测存在或不存在检测物质来抑制IPF1和所述蛋白质的结合，或者通过IPF1和所述蛋白质的结合产生的信号和/或标记的变化来抑制IPF1和所述蛋白质的结合，其中信号和 /或可以检测标记：（i）HNF3G，（ii）PHF1和（iii）DLX4。

4. 发明申请

US20050164198A1 Mutant sequence analyzer 审中-公开
标题翻译：突变序列分析仪
公开(公告)号：US20050164198A1
公开(公告)日：2005-07-28
申请号：US10513928
申请日：2003-05-12
申请人： Kensaku Imai , Hisayuki Horai , Hirofumi Doi
发明人： Kensaku Imai , Hisayuki Horai , Hirofumi Doi
IPC分类号： C12M1/00 , C12Q1/68 , G06F17/30 , G06F19/22 , H04R23/00 , G06F19/00 , G01N33/48 , G01N33/50
CPC分类号： H04R23/008 , G16B30/00
摘要： All DNA's of a mutant of a sequencing target organic species (e.g., a resistant bacterium, a tumor cell, or a virus) are extracted, and shotgun libraries are generated for the DNA's. DNA fragments are sequentially fetched from these libraries, and each fragment is subjected to sequencing using an automated DNA sequencer. Fragment sequence information such as base sequences of the respective DNA fragments of the mutant output from the sequencer is stored in a fragment sequence database.
摘要翻译：提取测序目标有机物种（例如抗性细菌，肿瘤细胞或病毒）的突变体的所有DNA，并为DNA产生猎枪文库。从这些文库顺序取出DNA片段，并使用自动化DNA测序仪对每个片段进行测序。片段序列信息，例如从定序器输出的突变体的各个DNA片段的碱基序列存储在片段序列数据库中。

5. 发明申请

US20050065082A1 C-jun phosphorylation inhibitors 审中-公开
标题翻译： C-jun磷酸化抑制剂
公开(公告)号：US20050065082A1
公开(公告)日：2005-03-24
申请号：US10509307
申请日：2003-03-31
申请人： Hirofumi Doi , Naoya Wada , Hiroto Nakajima
发明人： Hirofumi Doi , Naoya Wada , Hiroto Nakajima
IPC分类号： A61K38/17 , A61P25/00 , A61K38/52 , C12N9/99
CPC分类号： A61K38/1709
摘要： In the present invention, BMAL1, BPL1, KIAA1491 complete (SEQ ID NO: 1), and KIAA0596CT (SEQ ID NO:2), have a function for interacting with JNK3, wherein these peptides, as well as peptides derived therefrom can be used to inhibit c-Jun from being phosphorylated and exhibiting its functions (such as transcription activation activity). Inhibition of the phosphorylation of c-Jun suppresses apoptosis, such as nerve cell apoptosis. Thus, the present invention also provides a drug, a pharmaceutical composition and a method for use in preventing and/or treating a neurodegenerative disease (such as polyglutamine disease and Alzheimer's disease).
摘要翻译：在本发明中，BMAL1，BPL1，KIAA1491完整（SEQ ID NO：1）和KIAA0596CT（SEQ ID NO：2）具有与JNK3相互作用的功能，其中可以使用这些肽以及由其衍生的肽以抑制c-Jun被磷酸化并显示其功能（例如转录激活活性）。抑制c-Jun磷酸化抑制细胞凋亡，如神经细胞凋亡。因此，本发明还提供了用于预防和/或治疗神经退行性疾病（如聚谷氨酰胺病和阿尔茨海默病）的药物，药物组合物和方法。

6. 发明申请

US20070148150A1 MKK7 activation inhibitor 审中-公开
公开(公告)号：US20070148150A1
公开(公告)日：2007-06-28
申请号：US11705900
申请日：2007-02-14
申请人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
发明人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
IPC分类号： A61K38/54 , C12N9/99
CPC分类号： C07K14/47 , A61K38/1709 , G01N2500/00 , A61K2300/00
摘要： PAK4 and JIK, both of which bind to MKK7 and directly phosphorylate MKK7, were found in the present invention. The present invention provides an inhibitor of c-Jun phosphorylation caused by JNK3 and a method for inhibiting the same, and an agent for preventing and/or treating a disorder attributable to c-Jun phosphorylation caused by JNK3 and a method for preventing and/or treating the same, all of which comprise inhibiting one member selected from the following: the binding of PAK4 to MKK7, the phosphorylation of MKK7 by PAK4, the binding of JIK to MKK7, and the phosphorylation of MKK7 by JIK. Further, the present invention provides a method for identifying a compound that inhibits the binding of PAK4 to MKK7, the phosphorylation of MKK7 caused by PAK4, the binding of JIK to MKK7, or the phosphorylation of MKK7 caused by JIK, as well as the compound obtained thereby. Furthermore, the present invention provides a pharmaceutical composition containing an effective amount of at least one member selected from the group consisting of the aforementioned compound and the aforementioned inhibitor.

7. 发明申请

US20060172360A1 Mkk7 activation inhibitor 失效
标题翻译： Mkk7激活抑制剂
公开(公告)号：US20060172360A1
公开(公告)日：2006-08-03
申请号：US10519465
申请日：2003-06-27
申请人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
发明人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
IPC分类号： A61K38/54 , C12Q1/48
CPC分类号： C07K14/47 , A61K38/1709 , G01N2500/00 , A61K2300/00
摘要： PAK4 and JIK, both of which bind to MKK7 and directly phosphorylate MKK7, were found in the present invention. The present invention provides an inhibitor of c-Jun phosphorylation caused by JNK3 and a method for inhibiting the same, and an agent for preventing and/or treating a disorder attributable to c-Jun phosphorylation caused by JNK3 and a method for preventing and/or treating the same, all of which comprise inhibiting one member selected from the following: the binding of PAK4 to MKK7, the phosphorylation of MKK7 by PAK4, the binding of JIK to MKK7, and the phosphorylation of MKK7 by JIK. Further, the present invention provides a method for identifying a compound that inhibits the binding of PAK4 to MKK7, the phosphorylation of MKK7 caused by PAK4, the binding of JIK to MKK7, or the phosphorylation of MKK7 caused by JIK, as well as the compound obtained thereby. Furthermore, the present invention provides a pharmaceutical composition containing an effective amount of at least one member selected from the group consisting of the aforementioned compound and the aforementioned inhibitor.
摘要翻译：在本发明中发现PAK4和JIK两者都结合MKK7并直接磷酸化MKK7。本发明提供了由JNK3引起的c-Jun磷酸化抑制剂及其抑制方法，以及用于预防和/或治疗由JNK3引起的由c-Jun磷酸化引起的病症的药剂，以及用于预防和/或所有这些都包括抑制选自以下的一种：PAK4与MKK7的结合，PAK4的MKK7的磷酸化，JIK与MKK7的结合以及通过JIK的MKK7的磷酸化。此外，本发明提供了鉴定抑制PAK4与MKK7结合的化合物，由PAK4引起的MKK7的磷酸化，JIK与MKK7的结合或由JIK引起的MKK7的磷酸化的化合物的方法，以及化合物由此获得。此外，本发明提供含有有效量的选自上述化合物和上述抑制剂中的至少一种的药物组合物。

8. 发明申请

US20050037449A1 Agent for controlling circadian rhythm disorder 审中-公开
标题翻译：用于控制昼夜节律紊乱的药剂
公开(公告)号：US20050037449A1
公开(公告)日：2005-02-17
申请号：US10901923
申请日：2004-07-29
申请人： Hirofumi Doi , Naoya Wada
发明人： Hirofumi Doi , Naoya Wada
IPC分类号： A61K38/00 , A61K39/00 , A61K45/00 , A61P25/00 , C12Q1/48 , G01N33/68 , C12Q1/68 , A61K31/66
CPC分类号： G01N33/6893 , C12Q1/485 , G01N2500/02
摘要： A method for controlling circadian rhythm disorders is described, characterized by inhibiting the phosphorylation of BMAL1 by c-Jun N-terminal kinase 3 (JNK3) due to the interaction between JNK3 and BMAL1; a method for preventing and/or treating diseases caused by circadian rhythm disorders; and a method for identifying a compound that inhibit phosphorylation of BMAL1 by JNK3. Also provided are: an agent for controlling circadian rhythm disorders, having the above characteristics; an agent for treating and/or preventing diseases caused by circadian rhythm disorders; a compound obtained by the identification method described above; an agent for inhibiting the phosphorylation of BMAL1 by JNK3, containing the compound; an agent for recovering the suppressed transcriptional activity of the complexes containing BMAL1 and CLOCK and for inhibiting the phosphorylation the same, containing an agent for inhibiting the expression and/or function of JNK3; and a pharmaceutical composition containing one of these.
摘要翻译：描述了一种控制昼夜节律紊乱的方法，其特征在于由于JNK3与BMAL1之间的相互作用，通过c-Jun N-末端激酶3（JNK3）抑制BMAL1的磷酸化; 用于预防和/或治疗由昼夜节律紊乱引起的疾病的方法; 以及通过JNK3鉴定抑制BMAL1磷酸化的化合物的方法。还提供：具有上述特征的用于控制昼夜节律紊乱的药剂; 用于治疗和/或预防由昼夜节律紊乱引起的疾病的药剂; 通过上述鉴定方法获得的化合物; 用于抑制含有该化合物的JNK3的BMAL1磷酸化的试剂; 用于回收含有BMAL1和CLOCK的复合物的抑制转录活性并抑制其磷酸化的试剂，其含有抑制JNK3的表达和/或功能的试剂; 和含有这些之一的药物组合物。

9. 发明授权

US07195894B2 MKK7 activation inhibitor 失效
标题翻译： MKK7激活抑制剂
公开(公告)号：US07195894B2
公开(公告)日：2007-03-27
申请号：US10519465
申请日：2003-06-27
申请人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
发明人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
IPC分类号： C12N15/09
CPC分类号： C07K14/47 , A61K38/1709 , G01N2500/00 , A61K2300/00
摘要： PAK4 and JIK, both of which bind to MKK7 and directly phosphorylate MKK7, were found in the present invention. The present invention provides an inhibitor of c-Jun phosphorylation caused by JNK3 and a method for inhibiting the same, and an agent for preventing and/or treating a disorder attributable to c-Jun phosphorylation caused by JNK3 and a method for preventing and/or treating the same, all of which comprise inhibiting one member selected from the following: the binding of PAK4 to MKK7, the phosphorylation of MKK7 by PAK4, the binding of JIK to MKK7, and the phosphorylation of MKK7 by JIK. Further, the present invention provides a method for identifying a compound that inhibits the binding of PAK4 to MKK7, the phosphorylation of MKK7 caused by PAK4, the binding of JIK to MKK7, or the phosphorylation of MKK7 caused by JIK, as well as the compound obtained thereby. Furthermore, the present invention provides a pharmaceutical composition containing an effective amount of at least one member selected from the group consisting of the aforementioned compound and the aforementioned inhibitor.
摘要翻译：在本发明中发现PAK4和JIK两者都结合MKK7并直接磷酸化MKK7。本发明提供了由JNK3引起的c-Jun磷酸化抑制剂及其抑制方法，以及用于预防和/或治疗由JNK3引起的由c-Jun磷酸化引起的病症的药剂，以及用于预防和/或所有这些都包括抑制选自以下的一种：PAK4与MKK7的结合，PAK4的MKK7的磷酸化，JIK与MKK7的结合以及通过JIK的MKK7的磷酸化。此外，本发明提供了鉴定抑制PAK4与MKK7结合的化合物，由PAK4引起的MKK7的磷酸化，JIK与MKK7的结合或由JIK引起的MKK7的磷酸化的化合物的方法，以及化合物由此获得。此外，本发明提供含有有效量的选自上述化合物和上述抑制剂中的至少一种的药物组合物。

10. 发明授权

US06182057B2 Device, method, and program storage medium for executing genetic algorithm 失效
标题翻译：用于执行遗传算法的设备，方法和程序存储介质
公开(公告)号：US06182057B2
公开(公告)日：2001-01-30
申请号：US08990050
申请日：1997-12-12
申请人： Yasuhiro Kikuchi , Hirofumi Doi
发明人： Yasuhiro Kikuchi , Hirofumi Doi
IPC分类号： G06F1518
CPC分类号： G06N3/126
摘要： A genetic algorithm executing device, in which search of a genetic algorithm is improved, sets a distribution of characters at each position of character strings represent candidates of solution, obtain the degree of disorder at each position by the distributions of characters, set a larger mutation rate at the position of which degree of disorder is higher. This device performs a mutation operation on the character strings according to the mutation rates. This device generates the new character strings by selecting positions of which degrees of disorder are higher than a predetermined value, and changing the character at the selected positions.
摘要翻译：遗传算法执行装置，其中改进了遗传算法的搜索，设置了字符串每个位置处的字符分布表示解的候选，通过字符分布获得每个位置的无序程度，设置较大的突变在无序程度较高的位置的比率。该装置根据突变率对字符串进行突变操作。该装置通过选择无序程度高于预定值的位置并改变所选位置的字符来生成新的字符串。

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