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1. 发明申请

WO2003006482A3 USE OF SPECIFIC T2R TASTE RECEPTORS TO IDENTIFY COMPOUNDS THAT BLOCK BITTER TASTE 审中-公开
公开(公告)号：WO2003006482A3
公开(公告)日：2003-01-23
申请号：PCT/US2002/021602
申请日：2002-07-10
申请人： SENOMYX, INC. , PRONIN, Alexey , CONNOR, Judy , TANG, Huixian , KEUNG, Walter , SERVANT, Guy , ADLER, Jon, Elliot , O'CONNELL, Shawn , BRUST, Paul
发明人： PRONIN, Alexey , CONNOR, Judy , TANG, Huixian , KEUNG, Walter , SERVANT, Guy , ADLER, Jon, Elliot , O'CONNELL, Shawn , BRUST, Paul
IPC分类号： G01N33/567
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.

2. 发明申请

WO2003006482A2 USE OF SPECIFIC T2R TASTE RECEPTORS TO IDENTIFY COMPOUNDS THAT BLOCK BITTER TASTE 审中-公开
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：WO2003006482A2
公开(公告)日：2003-01-23
申请号：PCT/US2002/021602
申请日：2002-07-10
申请人： SENOMYX, INC. , PRONIN, Alexey , CONNOR, Judy , TANG, Huixian , KEUNG, Walter , SERVANT, Guy , ADLER, Jon, Elliot , O'CONNELL, Shawn , BRUST, Paul
发明人： PRONIN, Alexey , CONNOR, Judy , TANG, Huixian , KEUNG, Walter , SERVANT, Guy , ADLER, Jon, Elliot , O'CONNELL, Shawn , BRUST, Paul
IPC分类号： C07K
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。

3. 发明申请

WO2009025793A2 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 COMPOSITIONS AND USE THEREOF 审中-公开
标题翻译：识别符合组合物中双歧杆菌组合物的双特异度化合物的人类T2R受体，以及其在测定中的用途，以鉴定组合物中的禁止（块状）双歧杆菌组合物及其用途的化合物
公开(公告)号：WO2009025793A2
公开(公告)日：2009-02-26
申请号：PCT/US2008/009864
申请日：2008-08-19
申请人： SENOMYX, INC. , LI, Xiaodong , PATRON, Andrew , TACHDJIAN, Catherine , XU, Hong , LI, Qing , PRONIN, Alexey , SERVANT, Guy , ZHANG, Lan , BRADY, Thomas , DARMOHUSODO, Vincent , ARELLANO, Melissa , SELCHAU, Victor , CHING, Brett Weylan , KARANEWSKY, Donald S. , BRUST, Paul , LING, Jing , ZHAO, Wen , PRIEST, Chad
发明人： LI, Xiaodong , PATRON, Andrew , TACHDJIAN, Catherine , XU, Hong , LI, Qing , PRONIN, Alexey , SERVANT, Guy , ZHANG, Lan , BRADY, Thomas , DARMOHUSODO, Vincent , ARELLANO, Melissa , SELCHAU, Victor , CHING, Brett Weylan , KARANEWSKY, Donald S. , BRUST, Paul , LING, Jing , ZHAO, Wen , PRIEST, Chad
IPC分类号： C12Q1/68
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。

4. 发明申请

WO2008013969A2 IMPROVED CELL-BASED FLUORESCENT ASSAYS FOR IDENTIFYING ALPHA AND DELTA ENaC MODULATORS 审中-公开
标题翻译：改进的基于细胞的荧光分析用于鉴定ALPHA和DELTA ENaC调节子
公开(公告)号：WO2008013969A2
公开(公告)日：2008-01-31
申请号：PCT/US2007/016963
申请日：2007-07-30
申请人： SENOMYX, INC. , SERVANT, Guy , BRUST, Paul , RAY, Sumita , HUNG, Ning
发明人： SERVANT, Guy , BRUST, Paul , RAY, Sumita , HUNG, Ning
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，其测量在δHENaC增强子存在和不存在下在测试细胞中表达的δ或α人类上皮钠通道（ENaC）的钠电导活性。改进包括使测试细胞与一定量的钠离子接触，所述钠离子量通常为至少15mM至140mM，持续足够的时间，至少5分钟至1小时，在测试细胞针对至少一个推定的增强子进行筛选之前。令人惊讶地发现，这种钠预处理增强了测定灵敏度，尤其是使用膜电位的测定法或荧光测定法检测电导变化的离子敏感染料。这些增强剂化合物可用于调节（增强）咸味感觉和治疗涉及异常hENaC功能的疾病。

5. 发明申请

WO2007047127A2 OPTIMIZED TRPM8 NUCLEIC ACID SEQUENCES AND THEIR USE IN CELL BASED ASSAYS AND TEST KITS TO IDENTIFY TRPM8 MODULATORS 审中-公开
标题翻译：优化的TRPM8核酸序列及其在基于细胞的测定中的用途以及鉴定TRPM8调节剂的测试工具
公开(公告)号：WO2007047127A2
公开(公告)日：2007-04-26
申请号：PCT/US2006/038962
申请日：2006-10-04
申请人： SENOMYX, INC. , SERVANT, Guy , BRUST, Paul , MOYER, Bryan , LU, Min , ECHEVERRI, Fernando , DAHAN, David , ZOLLER, Mark , WILLIAMS, Mark , KIMMICH, Rachel , KAMDAR, Poonit , DITSCHUN, Tanya , PATRON, Andrew
发明人： SERVANT, Guy , BRUST, Paul , MOYER, Bryan , LU, Min , ECHEVERRI, Fernando , DAHAN, David , ZOLLER, Mark , WILLIAMS, Mark , KIMMICH, Rachel , KAMDAR, Poonit , DITSCHUN, Tanya , PATRON, Andrew
IPC分类号： E01C3/06
CPC分类号： C07K14/705
摘要： Modified human TRPM8 nucleic acid sequences which are efficiently expressed in human cells and cell-based assays and test kits containing same are provided. These assays identify TRPM8 modulators using cells that express a modified human TRPM8 nucleic acid sequence according to the invention, wherein said sequence has been modified relative to a wild-type human TRPM8 nucleic acid sequence in order to optimize ion channel expression in desired cells. Assays using these modified TRPM8 sequences have been shown to identify compounds that modulate the human TRPM8 ion channel better or comparably to known coolants such as menthol and icilin.
摘要翻译：提供了在人细胞中有效表达的修饰的人TRPM8核酸序列和基于细胞的测定法和含有其的测试试剂盒。这些测定使用表达根据本发明的修饰的人TRPM8核酸序列的细胞鉴定TRPM8调节剂，其中相对于野生型人TRPM8核酸序列已经修饰了所述序列，以便优化所需细胞中的离子通道表达。已经显示使用这些修饰的TRPM8序列的测定来鉴定与已知的冷却剂如薄荷醇和icilin更好或相当地调节人类TRPM8离子通道的化合物。

6. 发明申请

WO2010065863A2 ASSAYS FOR IDENTIFYING GENES ENCODING SALTY TASTE RECEPTORS AND MODULATORS 审中-公开
标题翻译：用于鉴定编码盐味受体和调节剂的基因的测定
公开(公告)号：WO2010065863A2
公开(公告)日：2010-06-10
申请号：PCT/US2009/066788
申请日：2009-12-04
申请人： SENOMYX, INC. , MOYER, Bryan , ZLOTNIK, Albert , HEVEZI, Peter , SOTO, Hortensia , LU, Min , GAO, Na , SAGANICH, Michael , DAHAN, Michael , LAITA, Bianca , SERVANT, Guy , BRUST, Paul , WILLIAMS, Mark
发明人： MOYER, Bryan , ZLOTNIK, Albert , HEVEZI, Peter , SOTO, Hortensia , LU, Min , GAO, Na , SAGANICH, Michael , DAHAN, Michael , LAITA, Bianca , SERVANT, Guy , BRUST, Paul , WILLIAMS, Mark
IPC分类号： A01K67/00 , C12Q1/68 , C12Q1/02 , C12N5/10 , C12N1/00
CPC分类号： G01N33/5008 , A01K2267/03 , C07K14/705 , G01N2333/705
摘要： The present invention relates to rationales for selecting salty taste receptors from a discrete set of taste specific genes disclosed infra by use of methods including electrophysiology, bioiirformatics, and quantitative gene expression assays using transgenic animals as well as functional assays wherein these salty taste receptors may be expressed alone or in association with other taste specific polypeptides such as TRPML3, PKD2L1 or GPRl 13. In addition the invention relates to the use of the identified salty taste receptors in assays, preferably high- throughput, in order to identify modulators which maybe used as flavor additives to modulate salty taste. Preferably, the invention provides high- throughput mammalian and medium- throughput oocyte- based electrophysiological assays for identifying human TRPML3 modulators, preferably TRPML3 enhancers. Compounds that modulate TRPML3 function in the assay are expected to affect salty taste in humans. The inventive electrophysiological assays, such as the two-electrode voltage-clamp technique, facilitate the identification of compounds which specifically modulate human TRPML3. The assays of the invention provide a robust screen useful to detect compounds that facilitate (enhance) or inhibit TRPML3 function. Compounds that enhance or block TRPML3 channel activity should thereby modulate salty taste. In addition, these compounds maybe used to regulate sodium excretion, urinary output and other biological functions relating to sodium levels. This invention relates to the elucidation that TRPML3 is involved in salty taste perception in primates including humans and likely other mammals (given the significance of sodium and other ions to physiological functions and conditions this phenotype is likely strongly conserved in different animals). The TRPML3 gene also modulates one or more of sodium metabolism, sodium excretion, blood pressure, fluid retention, cardiac function and urinary functions such as urine production and excretion.
摘要翻译：本发明涉及通过使用包括电生理学，生物信息学和使用转基因动物的定量基因表达测定法的方法从下文公开的一组离体味觉特异性基因中选择咸味受体的基本原理以及功能其中这些咸味受体可以单独表达或与其他味道特异性多肽例如TRPML3，PKD2L1或GPR113结合表达。另外，本发明涉及鉴定的咸味受体在测定中的用途，优选高通量为了鉴定可能用作香料添加剂来调节咸味的调节剂。优选地，本发明提供了用于鉴定人TRPML3调节剂，优选TRPML3增强子的高通量哺乳动物和中等通量的基于卵母细胞的电生理学测定法。期望在测定中调节TRPML3功能的化合物影响人类的咸味。本发明的电生理学测定法，例如双电极电压钳技术有助于鉴定特异性调节人TRPML3的化合物。本发明的测定法提供了用于检测促进（增强）或抑制TRPML3功能的化合物的有力筛选。因此增强或阻断TRPML3通道活性的化合物应调节咸味。此外，这些化合物可用于调节钠排泄，尿量和与钠水平有关的其他生物学功能。本发明涉及说明TRPML3参与包括人类和可能的其他哺乳动物（考虑到钠和其它离子对生理功能和条件的重要性，这种表型在不同动物中强烈保守）的灵长类中的咸味感知。 TRPML3基因还调节钠代谢，钠排泄，血压，体液潴留，心脏功能和泌尿功能如尿液产生和排泄中的一种或多种。

7. 发明申请

WO2004069191A2 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T1RS和T2RS的功能性联合，以及用于鉴定T1R和T2R调节剂的基于细胞的测定
公开(公告)号：WO2004069191A2
公开(公告)日：2004-08-19
申请号：PCT/US2004/002987
申请日：2004-02-03
申请人： SENOMYX INC. , SERVANT, Guy , OZECK, Mark , BRUST, Paul , XU, Hong
发明人： SERVANT, Guy , OZECK, Mark , BRUST, Paul , XU, Hong
IPC分类号： A61K
CPC分类号： G01N33/5041 , G01N33/5008 , G01N33/566 , G01N2333/726 , G01N2500/10
摘要： The invention resides in part in the discovery that G proteins other than Gα 15 couples to T1R and T2R taste receptors, particularly G i proteins such as G αi . 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 G i 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：本发明部分在于发现除了Galpha15之外的G蛋白与T1R和T2R味觉受体特别是Gi蛋白如Galphai偶联。与这一发现有关，本发明提供基于细胞的测定方法，用于鉴定调节特异性T1R或T2R味觉受体的活性或调节其他T1R或T2R调节剂对T1R或T2R活性的影响的化合物。这些测定方法优选检测推定的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Gi蛋白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。

8. 发明申请

WO2009139913A1 ASSAY USING TRPML3 (MCOLN3) SALTY TASTE RECEPTOR AND USE IN IDENTIFYING TASTE (SALTY) MODULATORS 审中-公开
标题翻译：使用TRPML3（MCOLN3）盐酸受体的鉴定和用于鉴定（SALTY）调味品的用途
公开(公告)号：WO2009139913A1
公开(公告)日：2009-11-19
申请号：PCT/US2009/003045
申请日：2009-05-15
申请人： SENOMYX, INC. , SERVANT, Guy , BRUST, Paul , WILLIAMS, Mark
发明人： SERVANT, Guy , BRUST, Paul , WILLIAMS, Mark
IPC分类号： G01N33/53 , G01N33/567
CPC分类号： G01N33/6872 , G01N2500/10
摘要： Novel and improved TRPML3 expressing cell lines and TRPML3 assays for identifying TRPML3 modulators (enhancers and blockers) by use of membrane potential, calcium sensitive and other dyes that permit detection of TRPML3 modulators by use of fluorescence detection are provided. The invention provides preferred assay conditions using specific buffers for loading such dyes and provides cell lines that express TRPML3 at basal levels sufficient to detect TRPML3 activity in the absence of induction. These assays are very reliable and sensitive and are demonstrated to identify different TRPML3 enhancers and blockers in high throughput format using FLIPR and VIPR devices.
摘要翻译：提供了新型和改进的TRPML3表达细胞系和TRPML3测定法，用于通过使用膜电位鉴定TRPML3调节剂（增强子和阻断剂），通过使用荧光检测允许检测TRPML3调节剂的钙敏感性和其它染料。本发明提供优选的测定条件，使用用于加载这些染料的特定缓冲液，并提供表达TRPML3的细胞系，其基础水平足以在不存在诱导的情况下检测TRPML3活性。这些测定是非常可靠和敏感的，并被证明使用FLIPR和VIPR设备识别不同的TRPML3增强子和高通量格式的阻断剂。

9. 发明申请

WO2009008950A2 IDENTIFICATION OF TRPML3 (MCOLN3) AS A SALTY TASTE RECEPTOR AND USE IN ASSAYS FOR IDENTIFYING TASTE (SALTY) MODULATORS AND/OR THERAPEUTICS THAT MODULATE SODIUM TRANSPORT, ABSORPTION OR EXCRETION AND/OR ALDOSTERONE AND/OR VASOPRESSIN PRODUCTION OR RELEASE 审中-公开
标题翻译：鉴定作为盐酸受体的TRPML3（MCOLN3）和用于鉴定调节运输，吸收或/或阿尔斯酮和/或维生素C生产或替代物的硫酸盐（SALTY）调节剂和/或治疗剂的测定中的用途
公开(公告)号：WO2009008950A2
公开(公告)日：2009-01-15
申请号：PCT/US2008/007101
申请日：2008-06-06
申请人： SENOMYX, INC. , MOYER, Bryan , ZLOTNIK, Albert , HEVEZI, Peter , SOTO, Hortensia , LU, Min , GAO, Na , SERVANT, Guy , BRUST, Paul , WILLIAMS, Mark , KALABAT, Dalia , WHITE, Evan, Carl
发明人： MOYER, Bryan , ZLOTNIK, Albert , HEVEZI, Peter , SOTO, Hortensia , LU, Min , GAO, Na , SERVANT, Guy , BRUST, Paul , WILLIAMS, Mark , KALABAT, Dalia , WHITE, Evan, Carl
IPC分类号： C40B30/04 , C12N5/10 , C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/136 , C12Q2600/158 , C40B30/04 , C40B40/10 , G01N33/5044 , G01N33/566 , G01N33/6872 , G01N2333/726 , G01N2500/10
摘要： The present invention relates to high-throughput mammalian and medium-throughput oocyte-based electrophysiological assays for identifying human TRPML3 modulators, preferably TRPML3 enhancers. Compounds that modulate TRPML3 function in the assay are expected to affect salty taste in humans. The inventive electrophysiological assays, such as the two-electrode voltage-clamp technique, facilitate the identification of compounds which specifically modulate human TRPML3. The assays of the invention provide a robust screen useful to detect compounds that facilitate (enhance) or inhibit TRPML3 function. Compounds that enhance or block TRPML3 channel activity should thereby modulate salty taste. In addition, these compounds may be used to regulate sodium excretion, urinary output and other biological functions relating to sodium levels. This invention relates to the elucidation that TRPML3 is involved in salty taste perception in primates including humans and likely other mammals (given the significance of sodium and other ions to physiological functions and conditions this phenotype is likely strongly conserved in different animals). The TRPML3 gene also modulates one or more of sodium metabolism, sodium excretion, blood pressure, fluid retention, cardiac function and urinary functions such as urine production and excretion. The inventors have identified TRPML3 as encoding a salty taste receptor in primates and humans (and likely other mammals) based on gene expression assays which have determined that TRPML3 is expressed specifically in taste bud cells and not in lingual epithelial cells, similar assays that have determined that TRPML3 is specifically expressed or enriched in the top half of taste bud cells in a subset of taste cells which do not express TRPM5 or PKD2L1, prior reports that document the expression of TRPML3 in other sensory organs such as the ear (therefore further substantiating the role of TRPML3 as a "professional" sensory gene), the strong expression of TRPML3 in the adrenal glands which play a strong role in regulation of sodium metabolism (as they regulate aldosterone a key molecule in sodium metabolism), and related thereto the fact that an autoimmune disease that elicits strong salt cravings, Addison's disease, involves destruction of the adrenal glands, and functional (electrophysiological) studies which indicate that TRPML3 conducts sodium and exhibits biochemical characteristics consistent with a human salty taste receptor (passes K+, Li+, and is amiloride-insensitive.) This application also discloses novel rationales and methods for identifying primate taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, as well as genes involved in sweet, bitter, umami, and sour taste and other taste perceptions including fat taste, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity. The genes identified using these methods, can be used in assays for identifying taste modulators (enhancers or blockers) and potential t
摘要翻译：本发明涉及用于鉴定人TRPML3调节剂（优选TRPML3增强子）的高通量哺乳动物和中等吞吐量的基于卵母细胞的电生理测定法。在测定中调节TRPML3功能的化合物预期会影响人体的咸味。本发明的电生理测定，例如双电极电压钳技术，有助于鉴定特异性调节人TRPML3的化合物。本发明的测定法提供了一种可用于检测促进（增强）或抑制TRPML3功能的化合物的稳健筛选。增强或阻断TRPML3通道活性的化合物应该调节咸味。此外，这些化合物可用于调节与钠水平相关的钠排泄，泌尿生产和其他生物功能。本发明涉及TRPML3涉及包括人和可能的其他哺乳动物在内的灵长类动物的咸味感知（给出钠和其它离子对生理功能和条件的重要性，该表型可能在不同动物中强烈保守）。 TRPML3基因还调节钠代谢，钠排泄，血压，流体保留，心脏功能和尿液功能如尿液产生和排泄中的一种或多种。发明人已经基于基因表达测定法将TrPML3鉴定为在灵长类动物和人类（以及可能的其他哺乳动物）中编码咸味受体，其已经确定TRPML3特异性地在味蕾细胞中表达，而不是在舌上皮细胞中表达， TRPML3在不表达TRPM5或PKD2L1的味觉细胞的子集中的特定表达或富集的上半部分的浓度中，先前报道了TRPML3在其他感觉器官如耳朵中的表达（因此进一步证实了 TRPML3作为“专业”感觉基因的作用），TRPML3在钠代谢调节中起重要作用的肾上腺中的强烈表达（因为它们调节醛固酮是钠代谢中的关键分子），与此相关的事实是引起强烈渴望的自身免疫性疾病艾迪生病涉及肾上腺的破坏和功能性（电极这些研究表明TRPML3可以进行钠化，并具有与人类咸味受体一致的生物化学特性（通过K +，Li +，而且是阿米洛利不敏感的）。本申请还公开了识别灵长类动物特异性基因的新理论和方法，包括涉及咸味感知的基因，特别是人类咸味感知，以及涉及甜味，苦味，鲜味和酸味以及其它味道感觉（包括脂肪味道）的基因，以及涉及其它味觉细胞或味觉受体相关活性的基因，例如消化功能和消化相关疾病，滋味细胞周转，口服和消化道的免疫调节，以及糖尿病和肥胖等代谢调节。使用这些方法鉴定的基因可用于鉴定味觉调节剂（增强子或阻断剂）和潜在t的测定

10. 发明申请

WO2008153881A1 NOVEL CELL-BASED ASSAYS FOR INDENTIFYING ENHANCERS OR INHIBITORS OF T1R TASTE RECEPTORS (T1R2/T1R3 SWEET) AND UMAMI (T1R1/T1R3 UMAMI) TASTE RECEPTORS 审中-公开
标题翻译：用于补充T1R TASTE受体（T1R2 / T1R3 SWEET）和UMAMI（T1R1 / T1R3 UMAMI）药物受体的增强剂或抑制剂的新基于细胞的测定
公开(公告)号：WO2008153881A1
公开(公告)日：2008-12-18
申请号：PCT/US2008/007035
申请日：2008-06-04
申请人： SENOMYX, INC. , SERVANT, Guy , KAMDAR, Poonit , RIVADENEYRA, Adam
发明人： SERVANT, Guy , KAMDAR, Poonit , RIVADENEYRA, Adam
IPC分类号： A61K39/395
CPC分类号： G01N33/5008 , G01N2333/726
摘要： Improved assays for identifying modulators of sweet (TIR2/TIR3) and umami (TIRI/TIR3) taste receptors are disclosed These receptors may be the endogenous TIRs or may be functional variants such as chimeric taste receptors from the extracellular portion of one TIR or a variant or fragment thereof, and the transmembrane portion of another TIR or a variant or fragment thereof, preferably associated with a TIR3 polypeptide and a suitable G protein. The assays preferably use endogenous taste or gastrointestinal cells from mammalian cells or Xenopus oocytes which express TIR taste receptors or recombinant cell which express such TIRs. The modulators identified according to the assays are useful as taste modulators (which is confirmed in taste tests) and/or as therapeutics for treating conditions such as diabetes, obesity weight control, fat metabolism, glucose metabolism, insulin metabolism, satiety and/or the release of satiety peptides such as GLP-1.
摘要翻译：公开了用于鉴定甜味（TIR2 / TIR3）和鲜味（TIRI / TIR3）味觉感受器的调节剂的改进的测定法。这些受体可以是内源性TIR，或者可以是功能性变体，例如来自一个TIR或变体的胞外部分的嵌合味觉受体或其片段，以及另一TIR或其变体或片段的跨膜部分，优选与TIR3多肽和合适的G蛋白相关联。测定优选使用表达TIR味觉受体的哺乳动物细胞或非洲爪蟾卵母细胞的内源性味道或胃肠细胞或表达这种TIR的重组细胞。根据测定法鉴定的调节剂可用作味觉调节剂（其在味觉测试中被证实）和/或用作治疗诸如糖尿病，肥胖体重控制，脂肪代谢，葡萄糖代谢，胰岛素代谢，饱腹感和/或释放饱和肽如GLP-1。

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