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11. 发明申请

WO2003021225A2 METHOD FOR CLASSIFICATION OF ANTI-PSYCHOTIC DRUGS 审中-公开
标题翻译：抗精神病药物分类方法
公开(公告)号：WO2003021225A2
公开(公告)日：2003-03-13
申请号：PCT/US2002/027802
申请日：2002-09-03
申请人： THE ROCKEFELLER UNIVERSITY , THE KAROLINSKA INSTITUTE
发明人： GREENGARD, Paul , FISONE, Gilberto
IPC分类号： G01N
CPC分类号： C12Q1/42 , C12Q1/485 , G01N33/6872 , G01N33/6896 , G01N33/94 , G01N33/9406 , G01N33/946 , G01N33/9466 , G01N33/9473 , G01N33/948 , G01N2500/00 , G01N2800/302
摘要： The present invention provides a method for identifying an agent to be tested for an ability to treat a psychotic disorder in a patient in need of such treatment. The invention provides a method for screening candidate drugs for anti-psychotic drug activity, preferably atypical anti-psychotic activity, comprising contacting cells or tissues with a candidate drug, determining levels of phosphorylation of the intracellular signaling proteins, DARPP-32, ERK1, ERK2 and CREB, in said cells or tissues and determining the pattern of the levels of phosphorylation of the proteins. The pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB is, in certain embodiments, compared with the pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB in the presence of an atypical anti-psychotic drug.
摘要翻译：本发明提供了一种用于鉴定待测试试剂在治疗需要这种治疗的患者中治疗精神病的能力的方法。本发明提供了用于筛选候选药物用于抗精神病药物活性的方法，优选非典型抗精神病活性，包括使候选药物接触细胞或组织，确定细胞内信号传导蛋白DARPP-32，ERK1，ERK2的磷酸化水平和CREB，在所述细胞或组织中，并确定蛋白质的磷酸化水平的模式。在某些实施方案中，DARPP-32，ERK1，ERK2和CREB的磷酸化水平的模式与DARPP-32，ERK1，ERK2和CREB的磷酸化水平的模式相比，精神病药

12. 发明申请

WO2003020702A2 PHOSPHODIESTERASE ACTIVITY AND REGULATION OF PHOSPHODIESTERASE 1-B-MEDIATED SIGNALING IN BRAIN 审中-公开
标题翻译：大鼠磷酸二酯酶1-B介导的信号转导磷酸化酶活性及其调控
公开(公告)号：WO2003020702A2
公开(公告)日：2003-03-13
申请号：PCT/US2002/027803
申请日：2002-09-03
申请人： THE ROCKEFELLER UNIVERSITY , CHILDREN'S HOSPITAL MEDICAL CENTER
发明人： GREENGARD, Paul , REPASKE, David , SNYDER, Gretchen
IPC分类号： C07D
CPC分类号： G01N33/5041 , A61K31/00 , A61K31/137 , A61K31/55 , A61K49/0008 , C12Q1/44 , G01N33/9413 , G01N2333/916 , G01N2500/04 , G01N2800/2835
摘要： The present invention provides methods and compositions for modulating the activity of phosphodiesterase 1 B (PDE1B) in intracellular signaling pathways, including but not limited to, dopamine D1 intracellular signaling pathways. The invention also provides methods and compositions for modulating the activities of intracellular signaling molecules, including, but not limited to, DARPP-32 and GluR1 AMPA receptor, via modulation of PDE1B. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate PDE1B activity. The invention also provides methods of treating or ameliorating the symptoms of a disorder, including but not limited to a PDE1B-related disorder or a dopamine D1 receptor intracellular signaling pathway disorder, by administering a modulator of PDE1B, preferably, but not limited to, an inhibitor of PDE1B or an agent that decreases the production of PDE1B.
摘要翻译：本发明提供了用于调节细胞内信号传导途径（包括但不限于多巴胺D1细胞内信号传导途径）中磷酸二酯酶1B（PDE1B）活性的方法和组合物。本发明还提供了通过调节PDE1B来调节细胞内信号分子（包括但不限于DARPP-32和GluR1 AMPA受体）活性的方法和组合物。本发明还提供了药物组合物和筛选调节PDE1B活性的化合物的方法。本发明还提供了治疗或改善病症症状的方法，所述病症包括但不限于PDE1B相关病症或多巴胺D1受体细胞内信号传导病症，通过施用PDE1B调节剂，优选但不限于 PDE1B抑制剂或降低PDE1B产生的药剂。

13. 发明申请

WO1997003660A2 MODULATION OF PROTEIN PHOSPHATASE ACTIVITY AND USES RELATING TO FERTILITY AND CONTRACEPTION 审中-公开
标题翻译：蛋白磷酸酶活性的调节和与肥胖相关的使用
公开(公告)号：WO1997003660A2
公开(公告)日：1997-02-06
申请号：PCT/US1996011805
申请日：1996-07-17
申请人： THE ROCKEFELLER UNIVERSITY , OREGON REGIONAL PRIMATE RESEARCH CENTER, INC.
发明人： THE ROCKEFELLER UNIVERSITY , OREGON REGIONAL PRIMATE RESEARCH CENTER, INC. , FIGUEIREDO DA CRUZ E SILVA, Edgar , GREENGARD, Paul , VIJAYARAGHAVAN, Srinivasan , SMITH, Gary, Daniel
IPC分类号： A61K31/00
CPC分类号： A61K31/675 , A61K31/00 , A61K31/35
摘要： Mammalian sperm motility can be regulated by modulation of a protein phosphatase-1 (PP-1). Such modulation can be used to increase the fertility of individuals whose sperm are either immotile or submotile by treatment with a phosphatase inhibitor either in vitro or in vivo (during sperm maturation in the epididymis). Conversely, activators of GSK-3 activity which increase the phosphatase activity of motile sperm, can be utilized to decrease sperm motility and reduce the chances for reproductive success.
摘要翻译：哺乳动物精子活力可通过调节蛋白磷酸酶-1（PP-1）来调节。这种调节可用于通过在体外或体内（在附睾精子成熟期间）用磷酸酶抑制剂处理来增加精子是不动的或潜伏的个体的生育力。相反，增加活动精子的磷酸酶活性的GSK-3活性激活剂可用于降低精子活力并降低生殖成功的机会。

14. 发明公开

EP3369827A1 METHODS AND COMPOSITIONS FOR TRANSLATIONAL PROFILING AND MOLECULAR PHENOTYPING 有权
公开(公告)号：EP3369827A1
公开(公告)日：2018-09-05
申请号：EP18155000.5
申请日：2009-03-12
申请人： The Rockefeller University
发明人： HEINTZ, Nathaniel , GREENGARD, Paul , HEIMAN, Myriam , SCHAEFER, Anne , DOYLE, Joseph P.n , DOUGHERTY, Joseph D.
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/50
CPC分类号： C12N15/62 , A01K67/0278 , A01K2217/206 , A01K2227/105 , A01K2267/01 , C12N15/111 , C12N2320/12 , G01N33/5023 , G01N33/5058 , G01N2800/285
摘要： The invention provides methods and compositions are provided for translational profiling and molecular phenotyping of specific tissues, cells and cell subtypes of interest. The methods provided herein facilitate the analysis of gene expression in the selected subset present within a heterogeneous sample.

15. 发明申请

WO2011016861A3 NOVEL REGULATORY PROTEINS AND INHIBITORS 审中-公开
公开(公告)号：WO2011016861A3
公开(公告)日：2011-02-10
申请号：PCT/US2010/002173
申请日：2010-08-05
申请人： INTRA-CELLULAR THERAPIES, INC. , GREENGARD, Paul , LOU, Wenjie , HE, Gen , LI, Peng , WENNOGLE, Lawrence
发明人： GREENGARD, Paul , LOU, Wenjie , HE, Gen , LI, Peng , WENNOGLE, Lawrence
IPC分类号： C07K1/00 , C07K16/00 , C12P21/06
摘要： The disclosure provides a gamma secretase activating protein (gSAP) that activates gamma-secretase to produce beta-amyloid protein (A.beta). Deposition of A.beta has been associated with Alzheimer's disease and other pathologies. The disclosure further provides screening methods, research tools, inhibitors of gSAP, and methods of diagnosis, treatment and control of Alzheimer's disease as well as other neurodegenerative conditions associated with deposition of A.beta.

16. 发明申请

WO2003057165A3 COMPOSITIONS AND METHODS FOR PREVENTION AND TREATMENT OF AMYLOID-β PEPTIDE-RELATED DISORDERS 审中-公开
公开(公告)号：WO2003057165A3
公开(公告)日：2003-07-17
申请号：PCT/US2003/000249
申请日：2003-01-06
申请人： THE ROCKEFELLER UNIVERSITY
发明人： NETZER, William, J. , GREENGARD, Paul , XU, Huaxi
IPC分类号： A61K31/505
摘要： The present invention provides methods and compositions for modulating levels of amyloid-β peptide (Aβ) exhibited by cells or tissues. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate Aβ levels. The invention also provides modulation of Aβ levels via selective modulation ( e.g., inhibition) of ATP-dependent-γ-secretase activity. The invention also provides methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an Aβ-related disorder, by administering a modulator of γ-secretase, including, but not limited to, a selective inhibitor of ATP-dependent γ-secretase activity or an agent that decreases the formation of active (or optimally active) γ-secretase. The invention also provides the use of inhibitors of ATP-dependent γ-secretase activity to prevent, treat or ameliorate the symptoms of Alzheimer's disease.

17. 发明申请

WO2003057165A2 COMPOSITIONS AND METHODS FOR PREVENTION AND TREATMENT OF AMYLOID-β PEPTIDE-RELATED DISORDERS 审中-公开
标题翻译：用于预防和治疗淀粉样β肽相关疾病的组合物和方法
公开(公告)号：WO2003057165A2
公开(公告)日：2003-07-17
申请号：PCT/US2003/000249
申请日：2003-01-06
申请人： THE ROCKEFELLER UNIVERSITY
发明人： NETZER, William, J. , GREENGARD, Paul , XU, Huaxi
IPC分类号： A61K
CPC分类号： G01N33/5058 , A61K31/506 , A61K31/519 , A61K45/06 , G01N33/5008 , G01N33/502 , G01N2333/4709 , G01N2800/2821 , A61K2300/00
摘要： The present invention provides methods and compositions for modulating levels of amyloid-β peptide (Aβ) exhibited by cells or tissues. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate Aβ levels. The invention also provides modulation of Aβ levels via selective modulation ( e.g., inhibition) of ATP-dependent-γ-secretase activity. The invention also provides methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an Aβ-related disorder, by administering a modulator of γ-secretase, including, but not limited to, a selective inhibitor of ATP-dependent γ-secretase activity or an agent that decreases the formation of active (or optimally active) γ-secretase. The invention also provides the use of inhibitors of ATP-dependent γ-secretase activity to prevent, treat or ameliorate the symptoms of Alzheimer's disease.
摘要翻译：本发明提供了调节淀粉样蛋白水平的方法和组合物。由细胞或组织表现的肽（A＆bgr）。本发明还提供药物组合物和筛选调节Aβ的化合物的方法; 水平。本发明还提供了A＆bgr的调制; ATP依赖性分泌酶活性的选择性调节（例如，抑制）。本发明还提供了通过施用分泌酶的调节剂（包括但不限于ATP的选择性抑制剂）来预防，治疗或改善病症症状的方法，包括但不限于A＆Bgr相关病症依赖性分泌酶活性或降低活性（或最佳活性）ϝ分泌酶形成的药剂。本发明还提供了ATP依赖性分泌酶活性抑制剂用于预防，治疗或改善阿尔茨海默病症状的用途。

18. 发明申请

WO2003021225A3 METHOD FOR CLASSIFICATION OF ANTI-PSYCHOTIC DRUGS 审中-公开
公开(公告)号：WO2003021225A3
公开(公告)日：2003-03-13
申请号：PCT/US2002/027802
申请日：2002-09-03
申请人： THE ROCKEFELLER UNIVERSITY , THE KAROLINSKA INSTITUTE
发明人： GREENGARD, Paul , FISONE, Gilberto
IPC分类号： C12Q1/48
摘要： The present invention provides a method for identifying an agent to be tested for an ability to treat a psychotic disorder in a patient in need of such treatment. The invention provides a method for screening candidate drugs for anti-psychotic drug activity, preferably atypical anti-psychotic activity, comprising contacting cells or tissues with a candidate drug, determining levels of phosphorylation of the intracellular signaling proteins, DARPP-32, ERK1, ERK2 and CREB, in said cells or tissues and determining the pattern of the levels of phosphorylation of the proteins. The pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB is, in certain embodiments, compared with the pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB in the presence of an atypical anti-psychotic drug.

19. 发明申请

WO1996035446A1 TREATMENT OF ALZHEIMER DISEASE BY MODULATION OF SYNAPSINS 审中-公开
标题翻译：通过调节SYNPSINS治疗阿尔茨海默病
公开(公告)号：WO1996035446A1
公开(公告)日：1996-11-14
申请号：PCT/US1996006835
申请日：1996-05-13
申请人： THE ROCKEFELLER UNIVERSITY , BRIGHAM AND WOMEN'S HOSPITAL
发明人： THE ROCKEFELLER UNIVERSITY , BRIGHAM AND WOMEN'S HOSPITAL , HAN, Hui-Quan , GREENGARD, Paul , KOSIK, Kenneth, S. , FERREIRA, Adriana
IPC分类号： A61K38/18
CPC分类号： A61K31/7076 , A61K38/185 , A61K38/1883
摘要： The role of synapsin II in both the reformation and the maintenance of synaptic connections in cultured hippocampal neurons can be the basis of therapy for neurodegenerative disorder, particularly Alzheimer disease, which involve the disruption of synapses. When synapsin II expression in neurons is blocked by antisense synapsin II oligonucleotides, the ability of hippocampal neurons to reform as well as to maintain synapses is severely disrupted. Antisense suppression of synapsin II after axon formation but immediately before synaptogenesis prevents synapse formation. Suppression of synapsin II after synaptogenesis disrupts the majority of existing synapses. Re-expression of synapsin II in synapsin deficient neurons achieved after removing the antisense oligonucleotides leads to the re-establishment of synaptic connections, providing direct evidence that synapsin II is required for the maintenance and/or restoration of synapses. Thus, therapeutic methods based on the reformation and the maintenance of synapses, including delivery of the synapsin cDNAS or proteins into the patient's nervous system, use of the synapsin cDNAS to promote the synapse forming ability of cells for grafting, and use of agents that increase the expression of, enhancing the activity of, or mimic the activity of, the endogenous synapsins, can provide treatment of neurodegenerative disorders.
摘要翻译：突触素II在培养的海马神经元的突触连接的重建和维持中的作用可以作为神经变性疾病，特别是涉及突触中断的阿尔茨海默氏病的治疗的基础。当突触素II在神经元中的表达被反义突触蛋白II寡核苷酸阻断时，海马神经元改变的能力以及维持突触的能力被严重地破坏。在突触形成之后但紧接在突触发生之前的突触体II的反义抑制阻止突触形成。突触后突触素II的抑制破坏了大多数现有的突触。在去除反义寡核苷酸后实现的突触素缺陷型神经元中突触素II的重新表达导致突触连接的重新建立，提供突触间质II用于维持和/或恢复突触所需的直接证据。因此，基于重建和维持突触的治疗方法，包括将突触素cDNAS或蛋白质递送到患者神经系统中，使用突触素cDNAS来促进细胞用于移植的突触形成能力，并且使用增加的试剂增强内源性突触素的活性或模拟活性的表达可提供治疗神经变性疾病。

20. 发明申请

WO1993011762A1 USE OF APP MODULATORS FOR THE MANUFACTURE OF A MEDICAMENT FOR THE TREATMENT OF AMYLOIDOSIS 审中-公开
标题翻译：用于制造治疗淀粉样变性的药物的APP调节剂的使用
公开(公告)号：WO1993011762A1
公开(公告)日：1993-06-24
申请号：PCT/US1992010961
申请日：1992-12-17
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , GANDY, Samuel, E. , CAPORASO, Gregg, L. , GREENGARD, Paul
IPC分类号： A61K31/335
CPC分类号： A61K31/70 , A61K31/365 , A61K31/47
摘要： Agents which modulate or affect the intracellular trafficking and processing of proteins in the mammalian cell can be utilized to affect the trafficking and processing of APP, thereby inhibiting production of Alzheimer type amyloidosis. Particularly useful agents are chloroquine and its related derivatives such as primaquine.

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