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1. 发明授权

US07829298B2 Human G protein-coupled receptors for metabolic-related disorders 有权
标题翻译：人G蛋白偶联受体代谢相关疾病
公开(公告)号：US07829298B2
公开(公告)日：2010-11-09
申请号：US10930662
申请日：2004-08-31
申请人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel T. Connolly , Huong T. Dang , Bryan J. Choi , James N. Leonard , Yaron Hakak , Chen W. Liaw , Dominic P. Behan , Derek T. Chalmers , Michael R. Lerner , Kevin P. Lowitz
发明人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel T. Connolly , Huong T. Dang , Bryan J. Choi , James N. Leonard , Yaron Hakak , Chen W. Liaw , Dominic P. Behan , Derek T. Chalmers , Michael R. Lerner , Kevin P. Lowitz
IPC分类号： G01N33/53
CPC分类号： C07D403/02 , A01K2217/00 , A01K2227/105 , A01K2267/03 , A61K31/4439 , C07K14/705 , G01N33/566 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.
摘要翻译：本发明涉及鉴定候选化合物是G蛋白偶联受体（GPCR）的调节剂的方法。在优选的实施方案中，GPCR是人。在其它优选实施方案中，GPCR与Gi偶联并降低细胞内cAMP的水平。在其它优选实施方案中，GPCR由脂肪细胞内源性表达。在进一步优选的实施方案中，GPCR抑制细胞内脂肪分解。在其它进一步优选的实施方案中，GPCR是烟酸受体。本发明还涉及使用所述GPCR的调节剂的方法。优选的调节剂是激动剂。本发明的激动剂可用作预防或治疗代谢相关疾病，包括血脂异常，动脉粥样硬化，冠心病，中风，胰岛素抵抗和2型糖尿病的治疗剂。

2. 发明授权

US06902902B2 Human G protein-coupled receptors and modulators thereof for the treatment of metabolic-related disorders 失效
公开(公告)号：US06902902B2
公开(公告)日：2005-06-07
申请号：US10314048
申请日：2002-12-06
申请人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel T. Connolly , Yaron Hakak , Dominic P. Behan , Derek T. Chalmers
发明人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel T. Connolly , Yaron Hakak , Dominic P. Behan , Derek T. Chalmers
IPC分类号： A61K31/4439 , G01N33/566 , G01N33/53 , C07H21/04 , C07K14/00
CPC分类号： C07D403/02 , A01K2217/00 , A01K2227/105 , A01K2267/03 , A61K31/4439 , C07K14/705 , G01N33/566 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.

3. 发明申请

US20110177612A1 Human G Protein-Coupled Receptors and Modulators Thereof for the Treatment of Metabolic-Related Disorders 审中-公开
标题翻译：人类G蛋白偶联受体及其调节剂用于治疗代谢相关性疾病
公开(公告)号：US20110177612A1
公开(公告)日：2011-07-21
申请号：US12881014
申请日：2010-09-13
申请人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel Connolly , Huong T. Dang , Bryan Choi , James Leonard , Yaron Hakak , Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Kevin P. Lowitz
发明人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel Connolly , Huong T. Dang , Bryan Choi , James Leonard , Yaron Hakak , Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Kevin P. Lowitz
IPC分类号： G01N33/68
CPC分类号： C07D403/02 , A01K2217/00 , A01K2227/105 , A01K2267/03 , A61K31/4439 , C07K14/705 , G01N33/566 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.
摘要翻译：本发明涉及鉴定候选化合物是G蛋白偶联受体（GPCR）的调节剂的方法。在优选的实施方案中，GPCR是人。在其它优选实施方案中，GPCR与Gi偶联并降低细胞内cAMP的水平。在其它优选实施方案中，GPCR由脂肪细胞内源性表达。在进一步优选的实施方案中，GPCR抑制细胞内脂肪分解。在其它进一步优选的实施方案中，GPCR是烟酸受体。本发明还涉及使用所述GPCR的调节剂的方法。优选的调节剂是激动剂。本发明的激动剂可用作预防或治疗代谢相关疾病，包括血脂异常，动脉粥样硬化，冠心病，中风，胰岛素抵抗和2型糖尿病的治疗剂。

4. 发明授权

US08691498B2 Methods of screening for a compound that reduces atherogenesis 失效
标题翻译：筛选减少动脉粥样化形成的化合物的方法
公开(公告)号：US08691498B2
公开(公告)日：2014-04-08
申请号：US11991232
申请日：2006-08-29
申请人： Yaron Hakak , David J. Unett , Joel Gatlin , Chen W. Liaw
发明人： Yaron Hakak , David J. Unett , Joel Gatlin , Chen W. Liaw
IPC分类号： C12Q1/00 , C12Q1/68 , C07K14/705
CPC分类号： G01N33/5041 , A61K38/1709 , A61K49/0008 , C07K14/47 , C07K14/723 , G01N33/6893 , G01N33/74 , G01N2333/726 , G01N2500/00 , G01N2800/32 , G01N2800/323
摘要： The present invention relates to methods of using a G protein-coupled receptor (GPCR) to identify whether a candidate compound is a modulator of atherogenesis. In certain embodiments, the GPCR couples to Gi. In certain embodiments, the GPCR is human. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of atherosclerosis and atherosclerotic disease, including coronary artery disease, myocardial infarction, peripheral arterial disease, and ischemic stroke. Agonists of the invention are additionally useful as therapeutic agents for the prevention or treatment of conditions related to MCP-1 expression, including but not limited to rheumatoid arthritis, Crohn's disease, and multiple sclerosis.
摘要翻译：本发明涉及使用G蛋白偶联受体（GPCR）鉴定候选化合物是否是动脉粥样硬化形成调节剂的方法。在某些实施方案中，GPCR与Gi相连。在某些实施方案中，GPCR是人。本发明的激动剂可用作预防或治疗动脉粥样硬化和动脉粥样硬化疾病（包括冠状动脉疾病，心肌梗塞，外周动脉疾病和缺血性中风）的治疗剂。本发明的激动剂另外可用作预防或治疗与MCP-1表达相关的病症的治疗剂，包括但不限于类风湿性关节炎，克罗恩病和多发性硬化症。

5. 发明申请

US20100331238A1 Human G protein-coupled receptor and modulators thereof for the treatment of atherosclerosis and atherosclerotic disease and for the treatment of conditions related to MCP-1 expression 失效
标题翻译：人G蛋白偶联受体及其调节剂用于治疗动脉粥样硬化和动脉粥样硬化疾病以及治疗与MCP-1表达相关的病症
公开(公告)号：US20100331238A1
公开(公告)日：2010-12-30
申请号：US11991232
申请日：2006-08-29
申请人： Yaron Hakak , David J. Unett , Joel Gatlin , Chen W. Liaw
发明人： Yaron Hakak , David J. Unett , Joel Gatlin , Chen W. Liaw
IPC分类号： A61K38/17 , C12Q1/02 , C07K14/435 , A61P29/00 , A61P9/10
CPC分类号： G01N33/5041 , A61K38/1709 , A61K49/0008 , C07K14/47 , C07K14/723 , G01N33/6893 , G01N33/74 , G01N2333/726 , G01N2500/00 , G01N2800/32 , G01N2800/323
摘要： The present invention relates to methods of using a G protein-coupled receptor (GPCR) to identify whether a candidate compound is a modulator of atherogenesis. In certain embodiments, the GPCR couples to Gi. In certain embodiments, the GPCR is human. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of atherosclerosis and atherosclerotic disease, including coronary artery disease, myocardial infarction, peripheral arterial disease, and ischemic stroke. Agonists of the invention are additionally useful as therapeutic agents for the prevention or treatment of conditions related to MCP-1 expression, including but not limited to rheumatoid arthritis, Crohn's disease, and multiple sclerosis.
摘要翻译：本发明涉及使用G蛋白偶联受体（GPCR）鉴定候选化合物是否是动脉粥样硬化形成调节剂的方法。在某些实施方案中，GPCR与Gi相连。在某些实施方案中，GPCR是人。本发明的激动剂可用作预防或治疗动脉粥样硬化和动脉粥样硬化疾病（包括冠状动脉疾病，心肌梗塞，外周动脉疾病和缺血性中风）的治疗剂。本发明的激动剂另外可用作预防或治疗与MCP-1表达相关的病症的治疗剂，包括但不限于类风湿性关节炎，克罗恩病和多发性硬化症。

6. 发明申请

US20050154029A1 Human G protein-coupled receptors and modulators thereof for the treatment of metabolic-related disorders 有权
标题翻译：人G蛋白偶联受体及其调节剂用于治疗代谢相关疾病
公开(公告)号：US20050154029A1
公开(公告)日：2005-07-14
申请号：US10930662
申请日：2004-08-31
申请人： David Unett , Ruoping Chen , Jeremy Richman , Daniel Connolly , Huong Dang , Bryan Choi , James Leonard , Yaron Hakak , Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Kevin Lowitz
发明人： David Unett , Ruoping Chen , Jeremy Richman , Daniel Connolly , Huong Dang , Bryan Choi , James Leonard , Yaron Hakak , Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Kevin Lowitz
IPC分类号： A61K31/4439 , G01N33/566 , C07D43/02
CPC分类号： C07D403/02 , A01K2217/00 , A01K2227/105 , A01K2267/03 , A61K31/4439 , C07K14/705 , G01N33/566 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.
摘要翻译：本发明涉及鉴定候选化合物是G蛋白偶联受体（GPCR）的调节剂的方法。在优选的实施方案中，GPCR是人。在其它优选实施方案中，GPCR与Gi偶联并降低细胞内cAMP的水平。在其它优选实施方案中，GPCR由脂肪细胞内源性表达。在进一步优选的实施方案中，GPCR抑制细胞内脂肪分解。在其它进一步优选的实施方案中，GPCR是烟酸受体。本发明还涉及使用所述GPCR的调节剂的方法。优选的调节剂是激动剂。本发明的激动剂可用作预防或治疗代谢相关疾病，包括血脂异常，动脉粥样硬化，冠心病，中风，胰岛素抵抗和2型糖尿病的治疗剂。

7. 发明申请

US20070079392A1 Human G protein-coupled receptors and modulators thereof for the treatment of metabolic-related disorders 审中-公开
标题翻译：人G蛋白偶联受体及其调节剂用于治疗代谢相关疾病
公开(公告)号：US20070079392A1
公开(公告)日：2007-04-05
申请号：US11603625
申请日：2006-11-22
申请人： Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Huong Dang , Bryan Choi , James Leonard , Yaron Hakak , Kevin Lowitz , David Unett , Ruoping Chen , Jeremy Richman , Daniel Connolly
发明人： Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Huong Dang , Bryan Choi , James Leonard , Yaron Hakak , Kevin Lowitz , David Unett , Ruoping Chen , Jeremy Richman , Daniel Connolly
IPC分类号： A01K67/027 , G01N33/53 , C12P21/06 , C07D403/02 , C07K14/705
CPC分类号： C07D403/02 , A01K2217/00 , A01K2227/105 , A01K2267/03 , A61K31/4439 , C07K14/705 , G01N33/566 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.
摘要翻译：本发明涉及鉴定候选化合物是G蛋白偶联受体（GPCR）的调节剂的方法。在优选的实施方案中，GPCR是人。在其它优选实施方案中，GPCR与Gi偶联并降低细胞内cAMP的水平。在其它优选实施方案中，GPCR由脂肪细胞内源性表达。在进一步优选的实施方案中，GPCR抑制细胞内脂肪分解。在其它进一步优选的实施方案中，GPCR是烟酸受体。本发明还涉及使用所述GPCR的调节剂的方法。优选的调节剂是激动剂。本发明的激动剂可用作预防或治疗代谢相关疾病，包括血脂异常，动脉粥样硬化，冠心病，中风，胰岛素抵抗和2型糖尿病的治疗剂。

8. 发明申请

US20050004178A1 Human G protein-coupled receptors and modulators thereof for the treatment of metabolic-related disorders 审中-公开
公开(公告)号：US20050004178A1
公开(公告)日：2005-01-06
申请号：US10897815
申请日：2004-07-23
申请人： David Unett , Ruoping Chen , Jeremy Richman , Daniel Connolly , Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Huong Dang , Bryan Choi , James Leonard , Yaron Hakak , Kevin Lowitz
发明人： David Unett , Ruoping Chen , Jeremy Richman , Daniel Connolly , Chen Liaw , Dominic Behan , Derek Chalmers , Michael Lerner , Huong Dang , Bryan Choi , James Leonard , Yaron Hakak , Kevin Lowitz
IPC分类号： A61K31/4439 , G01N33/566 , G01N33/53
CPC分类号： C07D403/02 , A01K2217/00 , A01K2227/105 , A01K2267/03 , A61K31/4439 , C07K14/705 , G01N33/566 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.

9. 发明申请

US20100093604A1 Gpr43 and modulators thereof for the treatment of metabolic-related disorders 有权
标题翻译： Gpr43及其调节剂用于治疗代谢相关疾病
公开(公告)号：US20100093604A1
公开(公告)日：2010-04-15
申请号：US11663370
申请日：2005-09-21
申请人： James N. Leonard , Yaron Hakak
发明人： James N. Leonard , Yaron Hakak
IPC分类号： A61K38/28 , G01N33/53 , C07K14/62 , A61P3/10
CPC分类号： G01N33/566 , G01N33/6845 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to a method for identifying a metabolic stabilizing compound by: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is modulated, where a modulation in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound. In addition, the invention relates to a method for identifying a metabolic stabilizing compound, comprising: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is increased, wherein an increase in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound. Further, the invention relates to a method for identifying a metabolic stabilizing compound, comprising: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is decreased, wherein a decrease in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound.
摘要翻译：本发明涉及通过以下方式鉴定代谢稳定化合物的方法：a）使候选化合物与GPR43接触，和b）确定是否调节GPR43功能性，其中GPR43官能度的调节指示候选化合物是代谢稳定化复合。此外，本发明涉及用于鉴定代谢稳定化合物的方法，包括：a）使候选化合物与GPR43接触，和b）确定GPR43的功能是否增加，其中GPR43功能的增加指示候选化合物为代谢稳定化合物。此外，本发明涉及用于鉴定代谢稳定化合物的方法，其包括：a）使候选化合物与GPR43接触，和b）确定GPR43官能度是否降低，其中GPR43官能度的降低指示候选化合物为代谢稳定化合物。

10. 发明授权

US09017949B2 Method of screening for compounds useful in the treatment of insulin resistance, impaired glucose tolerance or diabetes 有权
标题翻译：筛选用于治疗胰岛素抵抗，葡萄糖耐量异常或糖尿病的化合物的方法
公开(公告)号：US09017949B2
公开(公告)日：2015-04-28
申请号：US11663370
申请日：2005-09-21
申请人： James N. Leonard , Yaron Hakak
发明人： James N. Leonard , Yaron Hakak
IPC分类号： G01N33/566 , G01N33/68
CPC分类号： G01N33/566 , G01N33/6845 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to a method for identifying a metabolic stabilizing compound by: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is modulated, where a modulation in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound. In addition, the invention relates to a method for identifying a metabolic stabilizing compound, comprising: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is increased, wherein an increase in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound. Further, the invention relates to a method for identifying a metabolic stabilizing compound, comprising: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is decreased, wherein a decrease in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound.
摘要翻译：本发明涉及通过以下方式鉴定代谢稳定化合物的方法：a）使候选化合物与GPR43接触，和b）确定是否调节GPR43功能性，其中GPR43官能度的调节指示候选化合物是代谢稳定化复合。此外，本发明涉及用于鉴定代谢稳定化合物的方法，包括：a）使候选化合物与GPR43接触，和b）确定GPR43的功能是否增加，其中GPR43功能的增加指示候选化合物为代谢稳定化合物。此外，本发明涉及用于鉴定代谢稳定化合物的方法，其包括：a）使候选化合物与GPR43接触，和b）确定GPR43官能度是否降低，其中GPR43官能度的降低指示候选化合物为代谢稳定化合物。

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