公开(公告)号：US08598171B2

公开(公告)日：2013-12-03

申请号：US13048459

申请日：2011-03-15

申请人： William Netzer ,  Paul Greengard ,  Huaxi Xu

发明人： William Netzer ,  Paul Greengard ,  Huaxi Xu

IPC分类号： A01N43/58 ,  A01N43/54 ,  A01N43/40 ,  A61K31/50 ,  A61K31/497 ,  A61K31/435 ,  C07D239/42 ,  C07D401/04

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： 本发明提供调节细胞或组织表现出的淀粉样蛋白-β肽（Abeta）水平的方法和组合物。 本发明还提供了用于筛选调节Aβ水平的化合物的药物组合物和方法。 本发明还通过ATP依赖性γ-分泌酶活性的选择性调节（例如抑制）来提供Aβ水平的调节。 本发明还提供通过施用γ-分泌酶的调节剂（包括但不限于ATP-选择性抑制剂）的方法来预防，治疗或改善病症症状，包括但不限于与Aβ相关的病症， 依赖性γ-分泌酶活性或降低活性（或最佳活性）γ-分泌酶形成的试剂。 本发明还提供了ATP依赖性γ-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。

公开(公告)号：US20110312093A1

公开(公告)日：2011-12-22

申请号：US13048459

申请日：2011-03-15

申请人： William NETZER ,  Paul Greengard ,  Huaxi Xu

发明人： William NETZER ,  Paul Greengard ,  Huaxi Xu

IPC分类号： C12N5/071

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; 通过ATP依赖性γ-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γ-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，包括但不限于有关疾病的方法 依赖性γ-分泌酶活性或降低活性（或最佳活性）γ-分泌酶形成的试剂。 本发明还提供了ATP依赖性γ-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。

公开(公告)号：US07910586B2

公开(公告)日：2011-03-22

申请号：US10337261

申请日：2003-01-06

申请人： William Netzer ,  Paul Greengard ,  Huaxi Xu

发明人： William Netzer ,  Paul Greengard ,  Huaxi Xu

IPC分类号： A01N43/58 ,  A01N43/54 ,  A01N43/40 ,  A01N43/42 ,  A61K31/50 ,  A61K31/435 ,  A61K31/44 ,  C07D239/42 ,  C07D401/04 ,  C07D471/04 ,  C07D471/22 ,  C07D487/04

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; 通过ATP依赖性γ-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γ-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，包括但不限于有关疾病的方法 依赖性γ-分泌酶活性或降低活性（或最佳活性）γ-分泌酶形成的试剂。 本发明还提供了ATP依赖性γ-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。

公开(公告)号：US20090233993A1

公开(公告)日：2009-09-17

申请号：US12399850

申请日：2009-03-06

申请人： Huaxi Xu ,  Limin Li ,  Francesca-Fang Liao ,  Yun-wu Zhang ,  Wu-bo Li ,  Paul Greengard ,  Stanley N. Cohen

发明人： Huaxi Xu ,  Limin Li ,  Francesca-Fang Liao ,  Yun-wu Zhang ,  Wu-bo Li ,  Paul Greengard ,  Stanley N. Cohen

IPC分类号： A61K31/7088 ,  C07H21/00 ,  C12N15/74 ,  C12P21/02 ,  C07K2/00 ,  C12N5/06 ,  A61P25/28 ,  G01N33/567

CPC分类号： C07K14/705 ,  A61K38/00 ,  G01N2333/91205 ,  G01N2800/2821

摘要： Disclosed herein are compositions and methods relating to peptides. The peptides can inhibit amyloid beta (Aβ) generation and reduce GSK-3 activities. Further provided are compositions and methods for treating or preventing, for example, Alzheimer's disease, cancer, and diabetes.

摘要翻译： 本文公开了与肽相关的组合物和方法。 肽可以抑制淀粉样蛋白β（Abeta）的产生并降低GSK-3活性。 还提供了用于治疗或预防例如阿尔茨海默病，癌症和糖尿病的组合物和方法。

公开(公告)号：US08470548B2

公开(公告)日：2013-06-25

申请号：US13335402

申请日：2011-12-22

申请人： Per Svenningsson ,  Paul Greengard

发明人： Per Svenningsson ,  Paul Greengard

IPC分类号： G01N33/53 ,  G01N33/567 ,  G01N33/542 ,  C12Q1/68

CPC分类号： C12Q1/6876 ,  A01K67/0275 ,  A01K67/0276 ,  A01K2217/052 ,  A01K2217/075 ,  A01K2217/20 ,  A01K2227/105 ,  A01K2267/0356 ,  A61K49/0008 ,  C07K14/4721 ,  C07K2319/41 ,  C12N15/8509 ,  C12N2830/003 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/158 ,  C12Q2600/178 ,  G01N33/68 ,  G01N33/6896 ,  G01N33/942 ,  G01N2333/46 ,  G01N2500/00 ,  G01N2500/04 ,  G01N2500/10 ,  G01N2800/30 ,  G01N2800/304 ,  Y10T436/143333

摘要： The present invention relates to the use of p11 as a drug target as well as a tool for the diagnosis, treatment and development of p11/5-HT receptor related disorders. The invention further relates to p11 knock-out animals as well as p11 transgenic animals and their use as models for the development of novel psychotherapeutic agents, and to methods of diagnosis, prophylaxis and treatment of p11/5-HT receptor related disorders.

摘要翻译： 本发明涉及p11作为药物靶的用途以及用于诊断，治疗和发展p11 / 5-HT受体相关病症的工具。 本发明还涉及p11敲除动物以及p11转基因动物及其作为开发新型精神治疗剂的模型的用途，以及诊断，预防和治疗p11 / 5-HT受体相关病症的方法。

公开(公告)号：US20100143361A1

公开(公告)日：2010-06-10

申请号：US12447080

申请日：2007-10-24

申请人： Marc Flajolet ,  Paul Greengard

发明人： Marc Flajolet ,  Paul Greengard

IPC分类号： A61K39/395 ,  C12Q1/68 ,  G01N33/53 ,  A61K31/713 ,  A61K31/7088 ,  A61K31/415 ,  A61K31/405 ,  A61P25/28

CPC分类号： A61K31/44 ,  A61K31/40 ,  A61K31/70

摘要： The invention provides methods for treating Aβ peptide related disorders such as Alzheimer's disease comprising administering a therapeutically effective amount of a CK1 modulator to a patient in need thereof.

摘要翻译： 本发明提供了治疗A＆Bgr的方法。 肽相关疾病如阿尔茨海默氏病包括向有需要的患者施用治疗有效量的CK1调节剂。

公开(公告)号：US09157906B2

公开(公告)日：2015-10-13

申请号：US12951775

申请日：2010-11-22

申请人： Paul Greengard ,  David Repaske ,  Gretchen Snyder

发明人： Paul Greengard ,  David Repaske ,  Gretchen Snyder

IPC分类号： C12Q1/00 ,  G01N33/573 ,  G01N33/50 ,  C12Q1/44 ,  G01N33/94 ,  A61K31/00 ,  A61K31/137 ,  A61K31/55 ,  A61K49/00

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 1B (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.

公开(公告)号：US20140107104A1

公开(公告)日：2014-04-17

申请号：US14006172

申请日：2012-03-22

申请人： Akinori Nishi ,  Katsunori Kobayashi ,  Tsuyoshi Miyakawa ,  Paul Greengard

发明人： Akinori Nishi ,  Katsunori Kobayashi ,  Tsuyoshi Miyakawa ,  Paul Greengard

IPC分类号： A61K31/55 ,  G01N33/50 ,  C12Q1/68 ,  A61K31/135

CPC分类号： A61K31/55 ,  A61K31/135 ,  A61K31/138 ,  A61K45/06 ,  C12Q1/68 ,  G01N33/5023 ,  G01N33/5088 ,  A61K2300/00

摘要： The present invention provides a combination medicine for treatment of depression, comprising a combination of (A1) an antidepressant and either (B1) a dopamine D1 receptor agonist or (C1) a dopamine D1 receptor antagonist; and a method for screening for an antidepressant that in combination with a dopamine D1 receptor agonist provides an improvement in treatment of depression, the method comprising the steps of: administering, to a mammal, (A2) a compound having an antidepressant action and (B1) a dopamine D1 receptor agonist, and detecting a greater increase in depression-related gene expression, dopamine D1 receptor expression and/or dopamine D1 receptor signaling in comparison with the case where (A2) the compound having an antidepressant action or (B1) the dopamine D1 receptor agonist is administered.

摘要翻译： 本发明提供了治疗抑郁症的组合药物，其包含（A1）抗抑郁药和（B1）多巴胺D1受体激动剂或（C1）多巴胺D1受体拮抗剂的组合; 以及与多巴胺D1受体激动剂组合提供抗抑郁药治疗改善的抗抑郁药的方法，所述方法包括以下步骤：向哺乳动物施用（A2）具有抗抑郁作用的化合物和（B1 ）多巴胺D1受体激动剂，并且与（A2）具有抗抑郁作用的化合物或（B1）的情况相比，检测抑制相关基因表达，多巴胺D1受体表达和/或多巴胺D1受体信号传导的更大增加 给予多巴胺D1受体激动剂。

公开(公告)号：US20110071049A1

公开(公告)日：2011-03-24

申请号：US12918761

申请日：2009-03-12

申请人： Nathaniel Heintz ,  Paul Greengard ,  Myriam Heiman ,  Anne Schaefer ,  Joseph P. Doyle ,  Joseph D. Dougherty

发明人： Nathaniel Heintz ,  Paul Greengard ,  Myriam Heiman ,  Anne Schaefer ,  Joseph P. Doyle ,  Joseph D. Dougherty

IPC分类号： C40B30/04 ,  C40B40/08 ,  C40B30/00 ,  C12Q1/68 ,  C12N15/63

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： 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.

摘要翻译： 提供了用于特定组织，细胞和感兴趣的细胞亚型的翻译分型和分子表型的方法和组合物。 本文提供的方法有助于分析异种样品中存在的所选子集中的基因表达。

公开(公告)号：US07320785B2

公开(公告)日：2008-01-22

申请号：US10218137

申请日：2002-08-12

申请人： Paul Greengard ,  Per Svenningsson ,  Sergey V. Rakhilin ,  Natalia Starkova

发明人： Paul Greengard ,  Per Svenningsson ,  Sergey V. Rakhilin ,  Natalia Starkova

IPC分类号： A61K49/00 ,  G01N33/53 ,  G01N33/567

CPC分类号： C12N9/16 ,  C12Y301/03016 ,  G01N33/566 ,  G01N33/6872 ,  G01N33/6896 ,  G01N2500/02 ,  G01N2500/04

摘要： The present invention provides methods and compositions for modulating the phosphorylation of DARPP-32 in a serotonergic receptor intracellular signaling pathway. The invention provides methods and compositions for modulating the activities of DARPP-32, casein kinase 1 (CK1), cyclin-dependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP-1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A) in cells or tissues. The invention provides methods of treating serotonergic intracellular signaling pathway disorders, e.g., depression. The invention provides methods of treating dopamine-related disorders. The invention provides methods of identifying agents that modulate the activities of serotonergic receptor intracellular signaling molecules, DARPP-32, casein kinase 1, cyclin-dependent kinase 5, AMPA receptors, protein phosphatase-1, protein phosphatase 2C, protein phosphatase 2B and/or protein phosphatase 2A, for use in such treatments. The invention also provides methods of modulating phosphorylation-dependent activation of AMPA receptors for use in such treatments.

摘要翻译： 本发明提供用于调节血清素受体细胞内信号传导途径中DARPP-32的磷酸化的方法和组合物。 本发明提供了用于调节DARPP-32，酪蛋白激酶1（CK1），细胞周期蛋白依赖性激酶5（Cdk5），AMPA受体，蛋白磷酸酶-1（PP-1），蛋白磷酸酶2C（PP2C） ，蛋白磷酸酶2B（PP2B）和/或蛋白磷酸酶2A（PP2A）在细胞或组织中。 本发明提供治疗5-羟色胺能细胞内信号传导途径障碍（例如抑郁症）的方法。 本发明提供了治疗多巴胺相关疾病的方法。 本发明提供了鉴定调节血清素受体细胞内信号传导分子，DARPP-32，酪蛋白激酶1，细胞周期蛋白依赖性激酶5，AMPA受体，蛋白磷酸酶-1，蛋白磷酸酶2C，蛋白磷酸酶2B和/或 蛋白质磷酸酶2A，用于这种治疗。 本发明还提供调节用于这种治疗的AMPA受体的磷酸化依赖性活化的方法。