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21. 发明申请

US20080268471A1 USE OF SPECIFIC T2R RECEPTORS TO IDENTIFY COMPOUNDS THAT BLOCK BITTER TASTE 有权
标题翻译：使用特异性T2R受体鉴别化合物
公开(公告)号：US20080268471A1
公开(公告)日：2008-10-30
申请号：US12041956
申请日：2008-03-04
申请人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
发明人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
IPC分类号： G01N33/53 , G01N33/566
CPC分类号： G01N33/566 , G01N2333/726 , G01N2500/02 , G01N2500/04 , G01N2500/10
摘要： Assays for identifying compounds that modulate, preferably inhibit bitter taste associated with the activation of hT2R4, hT2R44 and/or hT2R61 are provided. The compounds identified according to these assays should modulate, e.g., inhibit bitter taste associated with bitter tasting compounds including quinine, 6-nitrosaccharin, saccharin and/or denatonium. These compounds are useful additives for foods, beverages or medicinal preparationshaving a bitter taste.
摘要翻译：提供了用于鉴定调节，优选抑制与激活hT2R4，hT2R44和/或hT2R61相关的苦味的化合物的分析。根据这些测定法鉴定的化合物应调节，例如抑制与苦味化合物（包括奎宁，6-亚硝基糖精，糖精和/或丹参）相关的苦味。这些化合物是具有苦味的食品，饮料或药用制剂的有用添加剂。

22. 发明申请

US20110207937A1 Compounds that inhibit (block) bitter taste in composition and methods of making same 有权
标题翻译：在组合物中抑制（阻断）苦味的化合物及其制备方法
公开(公告)号：US20110207937A1
公开(公告)日：2011-08-25
申请号：US13051052
申请日：2011-03-18
申请人： Xiaodong LI , Andrew Patron , Catherine Tachdjian , Hong Xu , Qing Li , Alexey Pronin , Guy Servant , Lan Zhang , Thomas Brady , Vincent Darmohusodo , Melissa Arellano , Victor Selchau , Brett Weylan Ching , Donald S. Karanewsky , Paul Brust , Jing Ling , Wen Zhao , Chad Priest
发明人： Xiaodong LI , Andrew Patron , Catherine Tachdjian , Hong Xu , Qing Li , Alexey Pronin , Guy Servant , Lan Zhang , Thomas Brady , Vincent Darmohusodo , Melissa Arellano , Victor Selchau , Brett Weylan Ching , Donald S. Karanewsky , Paul Brust , Jing Ling , Wen Zhao , Chad Priest
IPC分类号： C07D413/14 , C07D413/06
CPC分类号： C07C311/17 , A23L27/86 , A61K8/46 , A61K8/466 , A61K8/4933 , A61K8/494 , A61K8/4973 , A61K8/498 , A61K8/4986 , A61K31/135 , A61K31/4439 , A61K31/485 , A61K31/60 , A61K31/704 , A61K45/06 , A61Q11/00 , C07C233/73 , C07C311/04 , C07C311/13 , C07C311/16 , C07C311/18 , C07C311/19 , C07C311/20 , C07C311/21 , C07C311/29 , C07C311/46 , C07C323/49 , C07C335/16 , C07C335/18 , C07D213/42 , C07D213/71 , C07D217/08 , C07D223/18 , C07D307/14 , C07D307/52 , C07D317/58 , C07D333/20 , C07D333/34 , A61K2300/00
摘要： The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds present in, e.g., coffee. Also, the invention relates to the discovery of specific compounds and compositions containing that function as bitter taste blockers and the use thereof as bitter taste blockers or flavor modulators in, e.g., coffee and coffee flavored foods, beverages and medicaments. Also, the present invention relates to the discovery of a compound that antagonizes numerous different human T2Rs and the use thereof in assays and as a bitter taste blocker in compositions for ingestion by humans and animals.
摘要翻译：本发明涉及T2R味觉受体家族中的特定人味受体对存在于例如咖啡中的特定苦味化合物的反应的发现。此外，本发明涉及含有作为苦味抑制剂的特定化合物和组合物的发现，以及其作为例如咖啡和咖啡风味食品，饮料和药物中的苦味抑制剂或风味调节剂的用途。此外，本发明涉及一种拮抗多种不同人类T2R的化合物的发现及其在测定中的用途以及用于摄取人类和动物的组合物中的苦味阻滞剂。

23. 发明申请

US20090274632A1 Identification of human T2R receptors that respond to bitter compounds that elicit the bitter taste in compositions, and the use thereof in assays to identify compounds that inhibit (block) bitter taste in composition and use thereof 有权
标题翻译：识别在组合物中引起苦味的苦味化合物作用的人类T2R受体的鉴定及其在测定中用于鉴定组合物中抑制（阻断）苦味的化合物及其用途的用途
公开(公告)号：US20090274632A1
公开(公告)日：2009-11-05
申请号：US12222918
申请日：2008-08-19
申请人： Xiaodong Li , Andrew Patron , Catherine Tachdjian , Hong Xu , Qing Li , Alexey Pronin , Guy Servant , Lan Zhang , Thomas Brady , Vincent Darmohusodo , Melissa Arellano , Victor Selchau , Brett Weylan Ching , Donald S. Karanewsky , Paul Brust , Jing Ling , Wen Zhao , Chad Priest
发明人： Xiaodong Li , Andrew Patron , Catherine Tachdjian , Hong Xu , Qing Li , Alexey Pronin , Guy Servant , Lan Zhang , Thomas Brady , Vincent Darmohusodo , Melissa Arellano , Victor Selchau , Brett Weylan Ching , Donald S. Karanewsky , Paul Brust , Jing Ling , Wen Zhao , Chad Priest
IPC分类号： A61K9/68 , G01N33/68 , C12Q1/02 , G01N33/53 , C07D261/06 , C07C65/00 , C07D307/02 , C07D413/02 , A61K31/192 , A61K31/7034 , A61K31/4439 , A61K31/55 , C07K14/435 , C07D241/36 , C07D263/54 , C07D213/62 , C07D223/18 , C07D239/72 , C07D487/02 , C07D413/14 , C07D403/14 , C07D233/00 , C07D249/12 , C07D251/02 , A61K31/4164 , A61K31/4196 , A61K31/53 , A61K31/42 , A61K8/49 , A61P27/00 , A61Q11/00
CPC分类号： C07C311/17 , A23L27/86 , A61K8/46 , A61K8/466 , A61K8/4933 , A61K8/494 , A61K8/4973 , A61K8/498 , A61K8/4986 , A61K31/135 , A61K31/4439 , A61K31/485 , A61K31/60 , A61K31/704 , A61K45/06 , A61Q11/00 , C07C233/73 , C07C311/04 , C07C311/13 , C07C311/16 , C07C311/18 , C07C311/19 , C07C311/20 , C07C311/21 , C07C311/29 , C07C311/46 , C07C323/49 , C07C335/16 , C07C335/18 , C07D213/42 , C07D213/71 , C07D217/08 , C07D223/18 , C07D307/14 , C07D307/52 , C07D317/58 , C07D333/20 , C07D333/34 , A61K2300/00
摘要： The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds present in, e.g., coffee. Also, the invention relates to the discovery of specific compounds and compositions containing that function as bitter taste blockers and the use thereof as bitter taste blockers or flavor modulators in, e.g., coffee and coffee flavored foods, beverages and medicaments. Also, the present invention relates to the discovery of a compound that antagonizes numerous different human T2Rs and the use thereof in assays and as a bitter taste blocker in compositions for ingestion by humans and animals.
摘要翻译：本发明涉及T2R味觉受体家族中的特定人味受体对存在于例如咖啡中的特定苦味化合物的反应的发现。此外，本发明涉及含有作为苦味抑制剂的特定化合物和组合物的发现，以及其作为例如咖啡和咖啡风味食品，饮料和药物中的苦味抑制剂或风味调节剂的用途。此外，本发明涉及一种拮抗多种不同人类T2R的化合物的发现及其在测定中的用途以及用于摄取人类和动物的组合物中的苦味阻滞剂。

24. 发明申请

US20090181404A1 Cell-based fluorescent assays for identifying alpha and delta EnaC modulators 有权
标题翻译：用于鉴定α和δEnaC调节剂的基于细胞的荧光测定
公开(公告)号：US20090181404A1
公开(公告)日：2009-07-16
申请号：US12301530
申请日：2007-07-30
申请人： Guy Servant , Paul Brust , Sumita Ray , Ning Hung
发明人： Guy Servant , Paul Brust , Sumita Ray , Ning Hung
IPC分类号： G01N33/53
CPC分类号： G01N33/6872 , G01N33/5008 , G01N33/566
摘要： This invention relates to improved electrophysiological assays that measure sodium conductance activity of a delta or alpha human epithelial sodium channel (ENaC) expressed in a test cell in the presence and absence of delta hENaC enhancers. The improvement comprises contacting the test cells with an amount of sodium ion, typically from at least 15 mM to 140 mM, for a time sufficient, e.g. for at least 5 minutes to an hour, prior to the test cells being screened against at least one putative enhancer. It has been surprisingly discovered that this sodium pretreatment enhances assay sensitivity, especially assays that use membrane potential or ion sensitive dyes that detect changes in conductance fluorimetrically. These enhancer compounds have potential application in modulating (enhancing) salty taste perception and for treating disorders involving aberrant hENaC function.
摘要翻译：本发明涉及改进的电生理测定法，其测量在存在和不存在δHENaC增强子的情况下在测试细胞中表达的δ或α人上皮钠通道（ENaC）的钠电导活性。该改进包括将测试细胞与一定量的钠离子（通常为至少15mM至140mM）接触足够的时间，例如，在至少5分钟至1小时之前，在测试细胞被针对至少一个推定的增强子进行筛选之前。已经惊奇地发现，这种钠预处理增强了测定灵敏度，特别是使用膜电位或离子敏感染料检测荧光测量电导的变化的测定法。这些增强剂化合物在调节（增强）咸味感觉和治疗涉及异常hENaC功能的病症中具有潜在应用。

25. 发明授权

US08148544B2 Compounds that inhibit (block) bitter taste in composition and methods of making same 有权
标题翻译：在组合物中抑制（阻断）苦味的化合物及其制备方法
公开(公告)号：US08148544B2
公开(公告)日：2012-04-03
申请号：US13051052
申请日：2011-03-18
申请人： Xiaodong Li , Andrew Patron , Catherine Tachdjian , Hong Xu , Qing Li , Alexey Pronin , Guy Servant , Lan Zhang , Thomas Brady , Vincent Darmohusodo , Melissa Arellano , Victor Selchau , Brett Weylan Ching , Donald S. Karanewsky , Paul Brust , Jing Ling , Wen Zhao , Chad Priest
发明人： Xiaodong Li , Andrew Patron , Catherine Tachdjian , Hong Xu , Qing Li , Alexey Pronin , Guy Servant , Lan Zhang , Thomas Brady , Vincent Darmohusodo , Melissa Arellano , Victor Selchau , Brett Weylan Ching , Donald S. Karanewsky , Paul Brust , Jing Ling , Wen Zhao , Chad Priest
IPC分类号： C07D261/06
CPC分类号： C07C311/17 , A23L27/86 , A61K8/46 , A61K8/466 , A61K8/4933 , A61K8/494 , A61K8/4973 , A61K8/498 , A61K8/4986 , A61K31/135 , A61K31/4439 , A61K31/485 , A61K31/60 , A61K31/704 , A61K45/06 , A61Q11/00 , C07C233/73 , C07C311/04 , C07C311/13 , C07C311/16 , C07C311/18 , C07C311/19 , C07C311/20 , C07C311/21 , C07C311/29 , C07C311/46 , C07C323/49 , C07C335/16 , C07C335/18 , C07D213/42 , C07D213/71 , C07D217/08 , C07D223/18 , C07D307/14 , C07D307/52 , C07D317/58 , C07D333/20 , C07D333/34 , A61K2300/00
摘要： The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds present in, e.g., coffee. Also, the invention relates to the discovery of specific compounds and compositions containing that function as bitter taste blockers and the use thereof as bitter taste blockers or flavor modulators in, e.g., coffee and coffee flavored foods, beverages and medicaments. Also, the present invention relates to the discovery of a compound that antagonizes numerous different human T2Rs and the use thereof in assays and as a bitter taste blocker in compositions for ingestion by humans and animals.
摘要翻译：本发明涉及T2R味觉受体家族中的特定人味受体对存在于例如咖啡中的特定苦味化合物的反应的发现。此外，本发明涉及含有作为苦味抑制剂的特定化合物和组合物的发现，以及其作为例如咖啡和咖啡风味食品，饮料和药物中的苦味抑制剂或风味调节剂的用途。此外，本发明涉及一种拮抗多种不同人类T2R的化合物的发现及其在测定中的用途以及用于摄取人类和动物的组合物中的苦味阻滞剂。

26. 发明申请

US20100317035A1 USE OF SPECIFIC T2R TASTE RECEPTORS TO IDENTIFY COMPOUNDS THAT BLOCK BITTER TASTE 有权
标题翻译：特异性T2R受体受体的鉴别鉴定化合物
公开(公告)号：US20100317035A1
公开(公告)日：2010-12-16
申请号：US12854570
申请日：2010-08-11
申请人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
发明人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
IPC分类号： G01N33/566
CPC分类号： G01N33/566 , G01N2333/726 , G01N2500/02 , G01N2500/04 , G01N2500/10
摘要： Assays for identifying compounds that modulate, preferably inhibit bitter taste associated with the activation of hT2R4, hT2R44 and/or hT2R61 are provided. The compounds identified according to these assays should modulate, e.g., inhibit bitter taste associated with bitter tasting compounds including quinine, 6-nitrosaccharin, saccharin and/or denatonium. These compounds are useful additives for foods, beverages or medicinal preparations having a bitter taste.
摘要翻译：提供了用于鉴定调节，优选抑制与激活hT2R4，hT2R44和/或hT2R61相关的苦味的化合物的分析。根据这些测定法鉴定的化合物应调节，例如抑制与苦味化合物（包括奎宁，6-亚硝基糖精，糖精和/或丹参）相关的苦味。这些化合物是具有苦味的食品，饮料或药物制剂的有用添加剂。

27. 发明授权

US08071320B2 Use of specific T2R taste receptors to identify compounds that block bitter taste 有权
标题翻译：使用特定的T2R味觉受体来鉴别抑制苦味的化合物
公开(公告)号：US08071320B2
公开(公告)日：2011-12-06
申请号：US12854570
申请日：2010-08-11
申请人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
发明人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
IPC分类号： G01N33/566 , C07K14/705
CPC分类号： G01N33/566 , G01N2333/726 , G01N2500/02 , G01N2500/04 , G01N2500/10
摘要： Assays for identifying compounds that modulate, preferably inhibit bitter taste associated with the activation of hT2R4, hT2R44 and/or hT2R61 are provided. The compounds identified according to these assays should modulate, e.g., inhibit bitter taste associated with bitter tasting compounds including quinine, 6-nitrosaccharin, saccharin and/or denatonium. These compounds are useful additives for foods, beverages or medicinal preparations having a bitter taste.
摘要翻译：提供了用于鉴定调节，优选抑制与激活hT2R4，hT2R44和/或hT2R61相关的苦味的化合物的分析。根据这些测定法鉴定的化合物应调节，例如抑制与苦味化合物（包括奎宁，6-亚硝基糖精，糖精和/或丹参）相关的苦味。这些化合物是具有苦味的食品，饮料或药物制剂的有用添加剂。

28. 发明授权

US07776561B2 Use of specific T2R receptors to identify compounds that block bitter taste 有权
标题翻译：使用特定的T2R受体来鉴定阻止苦味的化合物
公开(公告)号：US07776561B2
公开(公告)日：2010-08-17
申请号：US12041956
申请日：2008-03-04
申请人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
发明人： Alexey Pronin , Judy Connor , Huixian Tang , Walter Keung , Guy Servant , Jon Elliot Adler , Shawn O'Connell , Paul Brust
IPC分类号： G01N33/567 , C07K14/705
CPC分类号： G01N33/566 , G01N2333/726 , G01N2500/02 , G01N2500/04 , G01N2500/10
摘要： Assays for identifying compounds that modulate, preferably inhibit bitter taste associated with the activation of hT2R4, hT2R44 and/or hT2R61 are provided. The compounds identified according to these assays should modulate, e.g., inhibit bitter taste associated with bitter tasting compounds including quinine, 6-nitrosaccharin, saccharin and/or denatonium. These compounds are useful additives for foods, beverages or medicinal preparationshaving a bitter taste.
摘要翻译：提供了用于鉴定调节，优选抑制与激活hT2R4，hT2R44和/或hT2R61相关的苦味的化合物的分析。根据这些测定法鉴定的化合物应调节，例如抑制与苦味化合物（包括奎宁，6-亚硝基糖精，糖精和/或丹参）相关的苦味。这些化合物是具有苦味的食品，饮料或药用制剂的有用添加剂。

29. 发明申请

US20070037134A1 Functional coupling of T1Rs and T2Rs by Gi proteins, and cell-based assays for the identification of T1R and T2R modulators 审中-公开
标题翻译：通过Gi蛋白的T1R和T2Rs的功能偶联和用于鉴定T1R和T2R调节剂的基于细胞的测定
公开(公告)号：US20070037134A1
公开(公告)日：2007-02-15
申请号：US11395375
申请日：2006-04-03
申请人： Guy Servant , Mark Ozeck , Paul Brust , Hong Xu
发明人： Guy Servant , Mark Ozeck , Paul Brust , Hong Xu
IPC分类号： G01N33/567 , C12Q1/00
CPC分类号： G01N33/5008 , G01N33/5041 , G01N33/566 , G01N2333/726 , G01N2500/10
摘要： The invention resides in part in the discovery that G proteins other than Gα15 couples to T1R and T2R taste receptors, particularly Gi proteins such as Gαi. Related to this discovery, the invention provides cell-based assay methods for identifying compounds that modulate the activity of specific T1R or T2R taste receptors or which modulate the effect of other T1R or T2R modulators on T1R or T2R activity. These assay methods preferably detect the effect of a putative T1R or T2R modulator compound on MAPK activation cAMP accumulation, or adenylyl cyclase activity or another signaling pathway regulated by Gi proteins. The level of MAPK activation, cAMP accumulation or adenylyl cyclase is preferably determined by immunoassay methods that use ligands (monoclonal or polyclonal antibodies) that specifically bind an activated (phosphorylated) MAPK, cAMP, or adenylyl cyclase.
摘要翻译：本发明部分地在于以下发现：除了Galpha 15之外的G蛋白与T1R和T2R味觉受体，特别是GII蛋白（例如Gα- SUB>。与该发现有关，本发明提供用于鉴定调节特异性T1R或T2R味觉受体的活性的化合物的基于细胞的测定方法，或调节其它T1R或T2R调节剂对T1R或T2R活性的影响。这些测定方法优选检测推测的T1R或T2R调节剂化合物对MAPK激活cAMP积聚或腺苷酸环化酶活性或由蛋白质调节的另一信号传导途径的影响。 MAPK活化水平，cAMP积聚或腺苷酸环化酶优选通过使用特异性结合活化（磷酸化）MAPK，cAMP或腺苷酸环化酶的配体（单克隆或多克隆抗体）的免疫测定方法来确定。

30. 发明授权

US10048274B2 Electrophysiological assays using oocytes that express human ENaC and the use of phenamil to improve the effect of ENaC enhancers in assays using membrane potential reporting dyes 有权
公开(公告)号：US10048274B2
公开(公告)日：2018-08-14
申请号：US13206656
申请日：2011-08-10
申请人： Guy Servant , Hong Chang , Cyril Redcrow , Sumita Ray , Imran Clark , Bryan Moyer
发明人： Guy Servant , Hong Chang , Cyril Redcrow , Sumita Ray , Imran Clark , Bryan Moyer
IPC分类号： C12N5/10 , G01N33/68 , G01N33/50
摘要： In one aspect, the present invention relates to a mammalian cell-based high-throughput assay for the profiling and screening of human epithelial sodium channel (hENaC) cloned from a human kidney c-DNA library and is also expressed in other tissues including human taste tissue. The present invention further relates to amphibian oocyte-based medium-throughput electrophysiological assays for identifying human ENaC modulators, preferably ENaC enhancers. Compounds that modulate ENaC function in a cell-based ENaC assay are expected to affect salty taste in humans.

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