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1. 发明申请

WO2004094648A2 METHODS OF TREATING DISEASES RESPONSIVE TO INDUCTION OF APOPTOSIS AND SCREENING ASSAYS 审中-公开
标题翻译：治疗反应性感染和筛查测定的方法
公开(公告)号：WO2004094648A2
公开(公告)日：2004-11-04
申请号：PCT/US2004/011916
申请日：2004-04-19
申请人： CYTOVIA, INC. ET AL. , KASIBHATLA, Shailaja , CAI, Sui, Xiong , TSENG, Ben , JESSEN, Katayoun, Alavi , MALIARTCHOUK, Serguei , ENGLISH, Nicole, Marion , KUEMMERLE, Jared , KEMNITZER, William, E. , ZHANG, Han-Zhong
发明人： KASIBHATLA, Shailaja , CAI, Sui, Xiong , TSENG, Ben , JESSEN, Katayoun, Alavi , MALIARTCHOUK, Serguei , ENGLISH, Nicole, Marion , KUEMMERLE, Jared , KEMNITZER, William, E. , ZHANG, Han-Zhong
IPC分类号： C12Q
CPC分类号： G01N33/5011 , A61K31/729
摘要： The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to a Tail Interacting Protein Related Apoptosis Inducing Protein (TIPRAIP). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using TIPRAIP as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified TIPRAIP; or whole cell assays using cells with altered levels of TIPRAIP. The invention also contemplates use of 3-(4azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole or a substituted 3aryl-5-aryl-[1,2,4]-oxadiazole which bind TIPRAIP and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled 3-(4azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole (or a labeled substituted 3-aryl-5-aryl-[1,2,4]-oxadiazole) is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.
摘要翻译：本发明涉及治疗，预防或改善对动物中胱天蛋白酶级联诱导有反应的疾病的方法，包括向动物施用与尾部相互作用蛋白相关的细胞凋亡诱导蛋白（TIPRAIP）特异性结合的化合物。本发明还涉及可用于药物发现凋亡诱导化合物的筛选方法。特别地，筛选方法涉及使用TIPRAIP作为发现可用作抗癌剂的凋亡激活剂的靶标。本发明的筛选方法可以使用纯化或部分纯化的TIPRAIP的均质或异源结合测定; 或使用具有改变水平的TIPRAIP的细胞的全细胞测定。本发明还考虑使用3-（4-氮杂苯基）-5-（3-氯 - 噻吩-2-基） - [1,2,4] - 恶二唑或取代的3-芳基-5-芳基 - [1,2 ，4] - 恶二唑，其结合TIPRAIP，因此可用于产生用于药物发现的抗体。或者，标记3-（4-氮杂苯基）-5-（3-氯 - 噻吩-2-基） - [1,2,4] - 恶二唑（或标记的取代的3-芳基-5-芳基 - [1,2 ，4] - 恶二唑）用于药物发现的竞争性结合测定。这样的测定提供用于凋亡激活剂的化学文库的高通量筛选。

2. 发明申请

WO2004094647A3 METHODS OF TREATING DISEASES RESPONSIVE TO INDUCTION OF APOPTOSIS AND SCREENING ASSAYS 审中-公开
公开(公告)号：WO2004094647A3
公开(公告)日：2004-11-04
申请号：PCT/US2004/011915
申请日：2004-04-19
申请人： CYTOVIA, INC. , KASIBHATLA, Shailaja , CAI, Sui Xiong , TSENG, Ben , JESSEN, Katayoun Alavi , MALIARTCHOUK, Serguei , ENGLISH, Nicole, Marion , JIANG, Songchun , SIRISOMA, Nilantha Sudath , ZHANG, Han-Zhong , KUEMMERLE, Jared
发明人： KASIBHATLA, Shailaja , CAI, Sui Xiong , TSENG, Ben , JESSEN, Katayoun Alavi , MALIARTCHOUK, Serguei , ENGLISH, Nicole, Marion , JIANG, Songchun , SIRISOMA, Nilantha Sudath , ZHANG, Han-Zhong , KUEMMERLE, Jared
IPC分类号： A61K49/00
摘要： The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to one or more Apoptosis Inducing Proteins (AIPs). AIPs include Transferrin Receptor Related Apoptosis Inducing Proteins (TRRAIPs), Clathrin Heavy Chain Related Apoptosis Inducing Proteins (CHCRAIPs), IQ motif containing GTPase Activating Protein Related Apoptosis Inducing Proteins (IQGAPRAIPs), and Heat Shock Protein Related Apoptosis Inducing Proteins (HSPRAIPs). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using AIPs as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified AIPs; or whole cell assays using cells with altered levels of one or more AIPs. The invention also contemplates use of gambogic acid or GA-related compounds which bind AIPs and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled GA is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.

3. 发明申请

WO2004094648A3 METHODS OF TREATING DISEASES RESPONSIVE TO INDUCTION OF APOPTOSIS AND SCREENING ASSAYS 审中-公开
标题翻译：治疗反应性感染和筛查测定的方法
公开(公告)号：WO2004094648A3
公开(公告)日：2006-03-23
申请号：PCT/US2004011916
申请日：2004-04-19
申请人： CYTOVIA INC , KASIBHATLA SHAILAJA , CAI SUI XIONG , TSENG BEN , JESSEN KATAYOUN ALAVI , MALIARTCHOUK SERGUEI , ENGLISH NICOLE MARION , KUEMMERLE JARED , KEMNITZER WILLIAM E , ZHANG HAN-ZHONG
发明人： KASIBHATLA SHAILAJA , CAI SUI XIONG , TSENG BEN , JESSEN KATAYOUN ALAVI , MALIARTCHOUK SERGUEI , ENGLISH NICOLE MARION , KUEMMERLE JARED , KEMNITZER WILLIAM E , ZHANG HAN-ZHONG
IPC分类号： A61K31/47 , A61K38/00 , C12Q20060101 , A61K48/00 , A61K39/395 , C12Q1/68
CPC分类号： G01N33/5011 , A61K31/729
摘要： The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to a Tail Interacting Protein Related Apoptosis Inducing Protein (TIPRAIP). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using TIPRAIP as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified TIPRAIP; or whole cell assays using cells with altered levels of TIPRAIP. The invention also contemplates use of 3-(4azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole or a substituted 3aryl-5-aryl-[1,2,4]-oxadiazole which bind TIPRAIP and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled 3-(4azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole (or a labeled substituted 3-aryl-5-aryl-[1,2,4]-oxadiazole) is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.
摘要翻译：本发明涉及治疗，预防或改善对动物中胱天蛋白酶级联诱导有反应的疾病的方法，包括向动物施用与尾部相互作用蛋白相关的细胞凋亡诱导蛋白（TIPRAIP）特异性结合的化合物。本发明还涉及可用于药物发现凋亡诱导化合物的筛选方法。特别地，筛选方法涉及使用TIPRAIP作为发现可用作抗癌剂的凋亡激活剂的靶标。本发明的筛选方法可以使用纯化或部分纯化的TIPRAIP的均一或异源结合测定; 或使用具有改变的TIPRAIP水平的细胞的全细胞测定。本发明还考虑使用3-（4-氮杂苯基）-5-（3-氯 - 噻吩-2-基） - [1,2,4] - 恶二唑或取代的3-芳基-5-芳基 - [1,2 ，4] - 恶二唑，其结合TIPRAIP，因此可用于引发可用于药物发现的抗体。或者，标记3-（4-氮杂苯基）-5-（3-氯 - 噻吩-2-基） - [1,2,4] - 恶二唑（或标记的取代的3-芳基-5-芳基 - [1,2 ，4] - 恶二唑）用于药物发现的竞争性结合测定。这样的测定提供用于凋亡激活剂的化学文库的高通量筛选。

4. 发明申请

WO2004094647A2 METHODS OF TREATING DISEASES RESPONSIVE TO INDUCTION OF APOPTOSIS AND SCREENING ASSAYS 审中-公开
标题翻译：治疗反应性感染和筛查测定的方法
公开(公告)号：WO2004094647A2
公开(公告)日：2004-11-04
申请号：PCT/US2004011915
申请日：2004-04-19
申请人： CYTOVIA INC , KASIBHATLA SHAILAJA , CAI SUI XIONG , TSENG BEN , JESSEN KATAYOUN ALAVI , MALIARTCHOUK SERGUEI , ENGLISH NICOLE MARION , JIANG SONGCHUN , SIRISOMA NILANTHA SUDATH , ZHANG HAN-ZHONG , KUEMMERLE JARED
发明人： KASIBHATLA SHAILAJA , CAI SUI XIONG , TSENG BEN , JESSEN KATAYOUN ALAVI , MALIARTCHOUK SERGUEI , ENGLISH NICOLE MARION , JIANG SONGCHUN , SIRISOMA NILANTHA SUDATH , ZHANG HAN-ZHONG , KUEMMERLE JARED
IPC分类号： A61K31/352 , A61K38/17 , A61K49/00 , C07D493/20 , C07D519/00 , C12Q20060101 , C12Q
CPC分类号： A61K49/0052 , A61K31/352 , A61K49/0043 , A61K51/0412 , A61K51/0419 , A61K51/0421 , A61K51/0453 , A61K51/0495
摘要： The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to one or more Apoptosis Inducing Proteins (AIPs). AIPs include Transferrin Receptor Related Apoptosis Inducing Proteins (TRRAIPs), Clathrin Heavy Chain Related Apoptosis Inducing Proteins (CHCRAIPs), IQ motif containing GTPase Activating Protein Related Apoptosis Inducing Proteins (IQGAPRAIPs), and Heat Shock Protein Related Apoptosis Inducing Proteins (HSPRAIPs). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using AIPs as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified AIPs; or whole cell assays using cells with altered levels of one or more AIPs. The invention also contemplates use of gambogic acid or GA-related compounds which bind AIPs and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled GA is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.
摘要翻译：本发明涉及一种治疗，预防或改善对动物中胱天蛋白酶级联诱导起反应的疾病的方法，包括向动物施用与一种或多种凋亡诱导蛋白（AIP）特异性结合的化合物。 AIPs包括转铁蛋白受体相关凋亡诱导蛋白（TRRAIP），网格蛋白重链相关凋亡诱导蛋白（CHCRAIPs），包含GTPase激活蛋白相关凋亡诱导蛋白（IQGAPRAIPs）和热休克蛋白相关凋亡诱导蛋白（HSPRAIPs）的IQ基序。本发明还涉及可用于药物发现凋亡诱导化合物的筛选方法。特别地，筛选方法涉及使用AIP作为发现用作抗癌剂的凋亡激活剂的靶标。本发明的筛选方法可以使用纯化或部分纯化的AIPs进行均一或异源结合测定; 或使用具有改变水平的一种或多种AIP的细胞的全细胞测定。本发明还考虑使用结合AIP的葡萄糖酸或GA相关化合物，因此可以用于产生可用于药物发现的抗体。或者，标记的GA用于药物发现的竞争性结合测定。这样的测定提供用于凋亡激活剂的化学文库的高通量筛选。

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