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公开(公告)号：US07318917B2
公开(公告)日：2008-01-15
申请号：US10656897
申请日：2003-09-05
IPC分类号： A61K49/00 , A61K38/43 , C07D487/00 , C12N9/00 , C07K14/01
CPC分类号： G01N33/9406
摘要： The invention describes the finding that 4-(4-dimethylaminostyrl)-N-methylpyridinium or ASP+ is a fluorescent substrate that is transported by several neurotransmitter transporters. Provided are methods for the analysis of neurotransmitter transport and binding using ASP+. The invention also provides rapid methods for screening for modulators of neurotransmitter transport. As neurotransmitter transporter defects are associated with numerous neurological disorders, the invention also provides methods for treating neurotransmitter transport-associated defects/conditions using the modulators identified by the screening methods of the invention.
摘要翻译： 本发明描述了4-（4-二甲基氨基苯甲酰基）-N-甲基吡啶或ASP + +是通过几种神经递质转运蛋白转运的荧光底物的发现。 提供了使用ASP＆lt; SUP＆gt;分析神经递质转运和结合的方法。 本发明还提供用于筛选神经递质转运调节剂的快速方法。 由于神经递质转运蛋白缺陷与许多神经障碍有关，本发明还提供了使用通过本发明的筛选方法鉴定的调节剂治疗神经递质转运相关缺陷/病症的方法。
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公开(公告)号：US08647827B2
公开(公告)日：2014-02-11
申请号：US13111713
申请日：2011-05-19
IPC分类号： G01N33/53 , G01N33/567 , C12Q1/02
CPC分类号： G01N33/9406 , G01N33/502 , G01N33/6872
摘要： The invention is based on the finding that IDT307 and analogs thereof are fluorescent substrates transported by several neurotransmitter transporters. Provided are methods for the analysis of neurotransmitter transport and binding using IDT307 and its analogs. The invention also provides rapid methods for screening for modulators of neurotransmitter transport.
摘要翻译： 本发明基于IDT307及其类似物是由几种神经递质转运蛋白转运的荧光底物的发现。 提供了使用IDT307及其类似物分析神经递质转运和结合的方法。 本发明还提供用于筛选神经递质转运调节剂的快速方法。
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公开(公告)号：US20110229910A1
公开(公告)日：2011-09-22
申请号：US13111713
申请日：2011-05-19
CPC分类号： G01N33/9406 , G01N33/502 , G01N33/6872
摘要： The invention is based on the finding that IDT307 and analogs thereof are fluorescent substrates transported by several neurotransmitter transporters. Provided are methods for the analysis of neurotransmitter transport and binding using IDT307 and its analogs. The invention also provides rapid methods for screening for modulators of neurotransmitter transport.
摘要翻译： 本发明基于IDT307及其类似物是由几种神经递质转运蛋白转运的荧光底物的发现。 提供了使用IDT307及其类似物分析神经递质转运和结合的方法。 本发明还提供用于筛选神经递质转运调节剂的快速方法。
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公开(公告)号：US07439039B2
公开(公告)日：2008-10-21
申请号：US10884194
申请日：2004-07-02
CPC分类号： C07K14/47
摘要： The serotonin transporter (SERT) is a target of various therapeutic agents used in the treatment of neurological and neurodegenerative disorders. The present invention provides novel forms of SERT that lacks high affinity recognition of specific serotonin reuptake inhibitors (SSRIs). The present invention therefore provides a novel target for use in screening and model development that can aid both the discovery of new medications and the discovery of novel pathways impacted in parallel with SERT blockade. Such novel targets can help identify new SSRI's with unique modifications and lead to discovery of pathways that secondarily support the therapeutic activity of these agents.
摘要翻译： 血清素转运蛋白（SERT）是用于治疗神经和神经退行性疾病的各种治疗剂的靶标。 本发明提供了对特异性5-羟色胺再摄取抑制剂（SSRI）缺乏高亲和力识别的SERT的新型形式。 因此，本发明提供了用于筛选和模型开发的新靶标，其可以帮助新药物的发现和发现与SERT阻断并行的新途径。 这种新颖的靶标可以帮助鉴定新的SSRI的独特修饰，并导致二次支持这些药物治疗活性的途径的发现。
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公开(公告)号：US07094532B2
公开(公告)日：2006-08-22
申请号：US09750609
申请日：2000-12-28
申请人： David Robertson , Randy D. Blakely
发明人： David Robertson , Randy D. Blakely
CPC分类号： C12Q1/6883 , C12Q2600/156
摘要： Isolated polynucleotide molecules and peptides encoded by these molecules are used in the analysis of human norepinephrine (NE) transporter variants, as well as in diagnostic and therapeutic applications, relating to a human NE transporter polymorphism. By analyzing genomic DNA or amplified genomic DNA, or amplified cDNA derived from mRNA, it is possible to type a human NE transporter with regard to the human NE transporter polymorphism, for example, in the context of diagnosing and treating NE transport impairments, and disorders associated with NE transport impairments, such as orthostatic intolerance.
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公开(公告)号：US07947255B2
公开(公告)日：2011-05-24
申请号：US11832905
申请日：2007-08-02
CPC分类号： G01N33/9406 , G01N33/502 , G01N33/6872
摘要： The invention is based on the finding that IDT307 and analogs thereof are fluorescent substrates transported by several neurotransmitter transporters. Provided are methods for the analysis of neurotransmitter transport and binding using IDT307 and its analogs. The invention also provides rapid methods for screening for modulators of neurotransmitter transport.
摘要翻译： 本发明基于IDT307及其类似物是由几种神经递质转运蛋白转运的荧光底物的发现。 提供了使用IDT307及其类似物分析神经递质转运和结合的方法。 本发明还提供用于筛选神经递质转运调节剂的快速方法。
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公开(公告)号：US20090156530A1
公开(公告)日：2009-06-18
申请号：US12146188
申请日：2008-06-25
申请人： Randy D. Blakely , Uhna Sung
发明人： Randy D. Blakely , Uhna Sung
IPC分类号： A61K31/7088 , C07H21/04 , C12N5/10 , C12N15/63 , A01K67/00 , G01N33/567
CPC分类号： G01N33/9433 , C07K14/70571 , G01N33/502
摘要： The present invention provides norepinepherine transporter (NET) mutants which display altered phosphorylation at site T30 and altered receptor trafficking. Methods for the use of the NET mutants, e.g., screening of compounds which alter NET trafficking, are also provided. A transgenic animal such as a mouse may comprise a NET mutant of the present invention.
摘要翻译： 本发明提供了在位点T30显示改变的磷酸化并改变受体运输的去甲肾上腺素转运蛋白（NET）突变体。 还提供了使用NET突变体的方法，例如筛选改变NET转运的化合物。 转基因动物例如小鼠可以包含本发明的NET突变体。
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8.发明授权High affinity L-proline transporter polypeptides; antibodies and immunoassays specific for them 失效高亲和力L-脯氨酸转运蛋白多肽; 针对他们的抗体和免疫测定
公开(公告)号：US5759788A
公开(公告)日：1998-06-02
申请号：US753985
申请日：1996-12-03
IPC分类号： A61K38/00 , C07K14/47 , C07K14/705 , C12N15/12 , G01N33/53
CPC分类号： C07K14/47 , C07K14/705 , A61K38/00
摘要： The anatomical distribution, nucleic acid sequence, pharmacological properties, and inferred structural features of a cDNA encoding a high affinity, Na.sup.+ -dependent rat brain L-proline transporter is described. The expression of this carrier in subpopulations of putative glutamatergic pathways supports a specific role for L-proline in excitatory amino acid neurotransmission. The cloned transporter cDNA predicts a 637 amino acid protein with 12 putative transmembrane domains and exhibits 44%-45% amino acid sequence identity with other neurotransmitter transporters. These findings support a synaptic role for L-proline in specific excitatory pathways in the CNS. The sequence can be used for expression of the transporter molecule, to make probes for the same protein from other species and related proteins, in diagnostic assays, and to design functional and structural analogs for use in research and possible clinical treatments. The protein is useful in making antibodies, conducting research studies, and design of therapeutic transporter modulators for clinical treatments.
摘要翻译： 描述了编码高亲和力，Na +依赖性大鼠脑L-脯氨酸转运蛋白的cDNA的解剖分布，核酸序列，药理学性质和推断的结构特征。 该载体在推定的谷氨酸能途径的亚群中的表达支持L-脯氨酸在兴奋性氨基酸神经传递中的特异性作用。 克隆的转运蛋白cDNA预测具有12个推定的跨膜结构域的637个氨基酸的蛋白质，并且与其他神经递质转运体显示44％-45％的氨基酸序列同一性。 这些发现支持L-脯氨酸在CNS中特异性兴奋途径中的突触作用。 该序列可用于表达转运蛋白分子，在诊断测定中制备来自其他物种和相关蛋白质的相同蛋白质的探针，并设计用于研究和可能的临床治疗的功能和结构类似物。 该蛋白质可用于制备抗体，进行研究和设计用于临床治疗的治疗性转运蛋白调节剂。
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9.发明授权High affinity, brain-specific nucleic acids encoding a L-proline transporter, and vectors, and host cells comprising the same 失效编码L-脯氨酸转运蛋白的高亲和性，脑特异性核酸，和载体，以及包含其的宿主细胞
公开(公告)号：US5580775A
公开(公告)日：1996-12-03
申请号：US879617
申请日：1992-05-01
CPC分类号： C07K14/47 , C07K14/705 , A61K38/00
摘要： The anatomical distribution, nucleic acid sequence, pharmacological properties, and inferred structural features of a cDNA encoding a high affinity, Na.sup.+ -dependent rat brain L-proline transporter is described. The expression of this carrier in subpopulations of putative glutamatergic pathways supports a specific role for L-proline in excitatory amino acid neurotransmission. The cloned transporter cDNA predicts a 637 amino acid protein with 12 putative transmembrane domains and exhibits 44%-45% amino acid sequence identity with other neurotransmitter transporters. These findings support a synaptic role for L-proline in specific excitatory pathways in the CNS. The sequence can be used for expression of the transporter molecule, to make probes for the same protein from other species and related proteins, in diagnostic assays, and to design functional and structural analogs for use in research and possible clinical treatments. The protein is useful in making antibodies, conducting research studies, and design of therapeutic transporter modulators for clinical treatments.
摘要翻译： 描述了编码高亲和力，Na +依赖性大鼠脑L-脯氨酸转运蛋白的cDNA的解剖分布，核酸序列，药理学性质和推断的结构特征。 该载体在推定的谷氨酸能途径的亚群中的表达支持L-脯氨酸在兴奋性氨基酸神经传递中的特异性作用。 克隆的转运蛋白cDNA预测具有12个推定的跨膜结构域的637个氨基酸的蛋白质，并且与其他神经递质转运体显示44％-45％的氨基酸序列同一性。 这些发现支持L-脯氨酸在CNS的特异性兴奋途径中的突触作用。 该序列可用于表达转运蛋白分子，在诊断测定中制备来自其他物种和相关蛋白质的相同蛋白质的探针，并设计用于研究和可能的临床治疗的功能和结构类似物。 该蛋白质可用于制备抗体，进行研究和设计用于临床治疗的治疗性转运蛋白调节剂。
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10.发明授权公开(公告)号：US07531713B2
公开(公告)日：2009-05-12
申请号：US11029895
申请日：2005-01-05
申请人： Randy D. Blakely , Richard Nass , David Miller
发明人： Randy D. Blakely , Richard Nass , David Miller
CPC分类号： G01N33/5014 , A01K67/0336 , A01K2217/05 , A01K2227/703 , A01K2267/035 , A01K2267/0393 , C12N2830/008 , G01N33/5008 , G01N33/5058 , G01N2500/00
摘要： Provided are in vivo screening methods to detect and identify substances that affect neuronal viability, and/or prevent neurodegeneration, and/or confer neuroprotective effects The screening methods utilize recombinant C. elegans expressing a detectable marker in neuronal sub-groups and the use of neurotoxins specific to specific neuronal cells. Also provided are methods for identifying modulators of neurotransmitter transporters such as the dopamine transporter. Therefore, the invention provides methods for identifying substances that can be used in the prevention and therapy of neurodegenerative diseases.
摘要翻译： 提供了用于检测和鉴定影响神经元存活力和/或预防神经变性和/或赋予神经保护作用的物质的体内筛选方法。筛选方法利用在神经元亚组中表达可检测标记的重组秀丽隐杆线虫和神经毒素的使用 特异性的特定神经细胞。 还提供了用于鉴定神经递质转运蛋白如多巴胺转运蛋白的调节剂的方法。 因此，本发明提供了用于鉴定可用于预防和治疗神经变性疾病的物质的方法。
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