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    • 3. 发明申请
    • METHODS OF TREATING DISEASES RESPONSIVE TO INDUCTION OF APOPTOSIS AND SCREENING ASSAYS
    • 治疗反应性感染和筛查测定的方法
    • WO2004094648A2
    • 2004-11-04
    • PCT/US2004/011916
    • 2004-04-19
    • CYTOVIA, INC. ET AL.KASIBHATLA, ShailajaCAI, Sui, XiongTSENG, BenJESSEN, Katayoun, AlaviMALIARTCHOUK, SergueiENGLISH, Nicole, MarionKUEMMERLE, JaredKEMNITZER, William, E.ZHANG, Han-Zhong
    • KASIBHATLA, ShailajaCAI, Sui, XiongTSENG, BenJESSEN, Katayoun, AlaviMALIARTCHOUK, SergueiENGLISH, Nicole, MarionKUEMMERLE, JaredKEMNITZER, William, E.ZHANG, Han-Zhong
    • C12Q
    • G01N33/5011A61K31/729
    • 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.
    • 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。
    • 7. 发明申请
    • METHODS OF TREATING DISEASES RESPONSIVE TO INDUCTION OF APOPTOSIS AND SCREENING ASSAYS
    • 治疗反应性感染和筛查测定的方法
    • WO2004094648A3
    • 2006-03-23
    • PCT/US2004011916
    • 2004-04-19
    • CYTOVIA INCKASIBHATLA SHAILAJACAI SUI XIONGTSENG BENJESSEN KATAYOUN ALAVIMALIARTCHOUK SERGUEIENGLISH NICOLE MARIONKUEMMERLE JAREDKEMNITZER WILLIAM EZHANG HAN-ZHONG
    • KASIBHATLA SHAILAJACAI SUI XIONGTSENG BENJESSEN KATAYOUN ALAVIMALIARTCHOUK SERGUEIENGLISH NICOLE MARIONKUEMMERLE JAREDKEMNITZER WILLIAM EZHANG HAN-ZHONG
    • A61K31/47A61K38/00C12Q20060101A61K48/00A61K39/395C12Q1/68
    • G01N33/5011A61K31/729
    • 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.
    • 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。