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1. 发明申请

US20070259354A1 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：US20070259354A1
公开(公告)日：2007-11-08
申请号：US11536394
申请日：2006-09-28
申请人： Guy Servant , Paul Brust , Bryan Moyer , Min Lu , Fernando Echeverri , David Dahan , Mark Zoller , Mark Williams , Rachel Kimmich , Poonit Kamdar , Tanya Ditschun , Andrew Patron
发明人： Guy Servant , Paul Brust , Bryan Moyer , Min Lu , Fernando Echeverri , David Dahan , Mark Zoller , Mark Williams , Rachel Kimmich , Poonit Kamdar , Tanya Ditschun , Andrew Patron
IPC分类号： C12Q1/68 , C07H21/02 , C07H21/04 , C12N15/85 , C12N5/10
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，其中所述序列相对于野生型人类TRPM8核酸序列已被修饰，以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。

2. 发明申请

US20070161052A1 TRPM5 based assays and the use thereof for the identification of modulators of sweet, bitter or umami (savory) taste 审中-公开
标题翻译：基于TRPM5的测定及其用于鉴定甜味，苦味或鲜味（咸味）味道的调节剂的用途
公开(公告)号：US20070161052A1
公开(公告)日：2007-07-12
申请号：US11583086
申请日：2006-10-19
申请人： Guy Servant , Mark Williams , Andrew Patron , Poonit Kamdar , Qing Chen , Bryan Moyer , David Dahan , Tanya Ditschun , Sumita Ray , Amy Ligani
发明人： Guy Servant , Mark Williams , Andrew Patron , Poonit Kamdar , Qing Chen , Bryan Moyer , David Dahan , Tanya Ditschun , Sumita Ray , Amy Ligani
IPC分类号： G01N33/567
CPC分类号： E01C3/06 , G01N33/566
摘要： Robust cell based assays are provided that use cells that express wild-type or modified TRPM5 nucleic acid sequences in order to identify putative taste modulators, preferably sweet, bitter and umami taste modulators. The preferred assays use HEK-293 cells that express TRPM5, optionally at least one GPCR, preferably a taste specific GPCR, and a G protein that couples therewith. These assays detect TRPM5 modulators by use of membrane potential dyes that emit fluorescence on changes in TRPM5 activity based on changes in membrane potential and these changes in fluorescence are detectable using Fluorimetric Imaging Plate Readers (FLIPR).
摘要翻译：提供了基于稳健细胞的测定法，其使用表达野生型或修饰的TRPM5核酸序列的细胞，以鉴定推定的味道调节剂，优选甜味，苦味和鲜味调味剂。优选的测定法使用表达TRPM5，任选地至少一种GPCR，优选味道特异性GPCR的HEK-293细胞和与其偶联的G蛋白。这些测定法通过使用膜电位染料检测TRPM5调节剂，其基于膜电位的变化发射荧光的TRPM5活性的变化，并且使用荧光成像板读数器（FLIPR）检测这些荧光变化。

3. 发明申请

US20080305500A1 NOVEL CELL-BASED ASSAYS FOR IDENTIFYING 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：用于识别T1R TASTE RECEPTORS（T1R2 / T1R3 SWEET）和UMAMI（T1R1 / T1R3 UMAMI）TASTE RECEPTORS的增强剂或抑制剂的新细胞测定
公开(公告)号：US20080305500A1
公开(公告)日：2008-12-11
申请号：US11782336
申请日：2007-07-24
申请人： Guy Servant , Poonit Kamdar , Adam Rivadeneyra
发明人： Guy Servant , Poonit Kamdar , Adam Rivadeneyra
IPC分类号： G01N33/53 , G01N33/567 , G01N33/569
CPC分类号： G01N33/5008 , G01N2333/726
摘要： This invention relates to improved assays for identifying modulators (enhancers or inhibitors) of sweet (T1R2/T1R3) and umami (T1R1/T1R3) taste receptors. These receptors may comprise the endogenous T1Rs e.g., from humans or rodents, or may comprise functional variants such as chimeric taste receptors comprising the extracellular portion of one T1R or a variant or fragment thereof, either T1R1 or T1R2, and the transmembrane portion of another T1R or a variant or fragment thereof, either T1R1 or T1R2, preferably associated with a T1R3 polypeptide and a suitable G protein. The subject assays preferably use endogenous taste or gastrointestinal cells which express T1R taste receptors or recombinant cell which express such T1Rs, for example mammalian cells or Xenopus oocytes. The modulators (enhancers or inhibitors) identified according to the subject 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：本发明涉及用于鉴定甜味（T1R2 / T1R3）和鲜味（T1R1 / T1R3）味觉受体的调节剂（增强子或抑制剂）的改进测定法。这些受体可以包括例如来自人或啮齿动物的内源性T1R，或可以包含功能性变体，例如包含一个T1R的细胞外部分或其变体或片段，T1R1或T1R2的嵌合味觉受体，以及另一个T1R的跨膜部分或其变体或片段，T1R1或T1R2，优选与T1R3多肽和合适的G蛋白相关。主题分析优选使用表达T1R味觉受体的内源性味道或胃肠细胞或表达这种T1R的重组细胞，例如哺乳动物细胞或非洲爪蟾卵母细胞。根据主题测定鉴定的调节剂（增强剂或抑制剂）可用作味觉调节剂（其在味觉测试中得到证实）和/或用作治疗诸如糖尿病，肥胖症，体重控制，脂肪代谢，葡萄糖代谢，胰岛素代谢，饱腹感和/或饱和肽如GLP-1的释放。

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