JP2000506392A - 新規なヒト代謝指向型グルタミン酸レセプター - Google Patents
新規なヒト代謝指向型グルタミン酸レセプターInfo
- Publication number
- JP2000506392A JP2000506392A JP9540300A JP54030097A JP2000506392A JP 2000506392 A JP2000506392 A JP 2000506392A JP 9540300 A JP9540300 A JP 9540300A JP 54030097 A JP54030097 A JP 54030097A JP 2000506392 A JP2000506392 A JP 2000506392A
- Authority
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- Japan
- Prior art keywords
- nucleic acid
- seq
- receptor
- sequence
- metabotropic glutamate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/604,298 US6084084A (en) | 1996-02-21 | 1996-02-21 | Human metabotropic glutamate receptor |
| US08/604,298 | 1996-02-21 | ||
| PCT/US1997/009025 WO1997048724A2 (en) | 1996-02-21 | 1997-02-20 | Human metabotropic glutamate receptor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000506392A true JP2000506392A (ja) | 2000-05-30 |
| JP2000506392A5 JP2000506392A5 (cg-RX-API-DMAC10.html) | 2004-11-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9540300A Pending JP2000506392A (ja) | 1996-02-21 | 1997-02-20 | 新規なヒト代謝指向型グルタミン酸レセプター |
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|---|---|
| US (3) | US6084084A (cg-RX-API-DMAC10.html) |
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| IL (2) | IL125711A0 (cg-RX-API-DMAC10.html) |
| WO (1) | WO1997048724A2 (cg-RX-API-DMAC10.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008516606A (ja) * | 2004-10-14 | 2008-05-22 | カーネギー インスチチューション オブ ワシントン | 神経伝達物質センサーおよびそれを用いる方法 |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521297A (en) * | 1993-06-04 | 1996-05-28 | Salk Institute Biotechnology/Industrial Associates | Nucleic acids encoding human metabotropic glutamate receptors |
| CA2200606A1 (en) * | 1995-07-26 | 1997-02-13 | Nps Pharmaceuticals, Inc. | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors and the use of such compounds in the treatment of neurological disorders and diseases |
| US6221609B1 (en) | 1996-07-03 | 2001-04-24 | Eli Lilly And Company | Isolate nucleic acid encoding human MGLUR8 |
| US7262280B1 (en) | 1998-04-03 | 2007-08-28 | Nps Pharmaceuticals, Inc. | G-protein fusion receptors and constructs encoding same |
| JP2002510480A (ja) * | 1998-04-03 | 2002-04-09 | エヌピーエス ファーマシューティカルズ インコーポレーテッド | Ｇ−蛋白融合受容体およびキメラｇａｂａｂ受容体 |
| EP1662255A3 (en) * | 1998-08-18 | 2006-09-13 | The Johns Hopkins University School Of Medicine | Homer interacting proteins |
| JP2002523056A (ja) * | 1998-08-18 | 2002-07-30 | ザ ジョンズ ホプキンス ユニバーシティー スクール オブ メディシン | Ｈｏｍｅｒ相互作用タンパク質 |
| BR9913311A (pt) * | 1998-08-31 | 2001-10-16 | Trinity College Dublin | Molécula de ácido nucleico isolado, ácido nucleico isolado, vetor, proteìna, anticorpo e anti-soros formados contra uma proteìna, kit de diagnóstico, processos para reduzir a infecção de estafilococos coagulase-negativos de um dispositivo médico de retenção, para tratar uma infecção de estafilococus coagulase-negativa, para prevenir uma infecção de estafilococos coagulase-negativa em um paciente, para induzir uma resposta imunológica e para identificar compostos que inibem estafilococos coagulase-negativos |
| US20030185754A1 (en) * | 2001-01-16 | 2003-10-02 | Genset, S.A. | Treatment of CNS disorders using D-amino acid oxidase and D-aspartate oxidase antagonists |
| US20030166554A1 (en) * | 2001-01-16 | 2003-09-04 | Genset, S.A. | Treatment of CNS disorders using D-amino acid oxidase and D-aspartate oxidase antagonists |
| US6620850B2 (en) * | 2001-09-19 | 2003-09-16 | University Of Florida | Materials and methods for treatment of neurological disorders involving overactivation of glutamatergic ionotropic receptors |
| US20050233321A1 (en) * | 2001-12-20 | 2005-10-20 | Hess John W | Identification of novel polymorphic sites in the human mglur8 gene and uses thereof |
| EP1531855A4 (en) * | 2002-01-10 | 2009-07-22 | Osteotrophin Llc | TREATMENT OF BONE DISEASES WITH SKELETTAL ANABOLIKA |
| US20060252922A1 (en) * | 2002-12-04 | 2006-11-09 | Macina Roberto A | Compositions, splice variants and methods relating to colon specific genes and proteins |
| US20050186658A1 (en) * | 2003-10-17 | 2005-08-25 | Nps Pharmaceuticals, Inc. | Chimeric metabotropic glutamate receptors and uses thereof |
| WO2005073730A1 (en) * | 2004-01-31 | 2005-08-11 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with human metabotropic glutamate receptor 8 (mglur8) |
| TWI417095B (zh) | 2006-03-15 | 2013-12-01 | Janssen Pharmaceuticals Inc | １，４-二取代之３-氰基-吡啶酮衍生物及其作為ｍＧｌｕＲ２-受體之正向異位性調節劑之用途 |
| US8889950B2 (en) * | 2006-07-28 | 2014-11-18 | The George Washington University | Repression of AtGLR3.2 increases plant biomass |
| US7424876B2 (en) * | 2006-10-06 | 2008-09-16 | Ford Global Technologies, Llc | Pushrod engine with multiple independent lash adjusters for each pushrod |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| MY152078A (en) | 2007-09-14 | 2014-08-15 | Ortho Mcneil Janssen Pharm | 1',3'-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2h,1'h-[1,4']bipyridinyl-2'-ones |
| CA2707309A1 (en) | 2007-12-18 | 2009-06-25 | Acumen Pharmaceuticals, Inc. | Novel addl receptor polypeptides, polynucleotides and host cells for recombinant production |
| CN102159713A (zh) * | 2008-05-20 | 2011-08-17 | Eos神经科学公司 | 用于递送光敏蛋白的载体和使用方法 |
| AU2009289784B2 (en) | 2008-09-02 | 2012-03-22 | Addex Pharma S.A. | 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors |
| WO2010060589A1 (en) | 2008-11-28 | 2010-06-03 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| AU2010246609B2 (en) | 2009-05-12 | 2013-09-05 | Addex Pharma S.A. | 1,2,4-triazolo [4,3-a] pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders |
| NZ596053A (en) | 2009-05-12 | 2013-05-31 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| EP2643320B1 (en) | 2010-11-08 | 2015-03-04 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| CN103298810B (zh) | 2010-11-08 | 2016-03-16 | 杨森制药公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| DK3096790T3 (da) | 2014-01-21 | 2019-10-07 | Janssen Pharmaceutica Nv | Kombinationer omfattende positive allosteriske modulatorer eller orthosteriske agonister af metabotrop glutamaterg subtype 2-receptor og anvendelse af disse |
| KR20220038826A (ko) | 2014-01-21 | 2022-03-29 | 얀센 파마슈티카 엔.브이. | 대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도 |
| EP3331564B1 (en) | 2015-08-07 | 2025-01-08 | Imaginab, Inc. | Antigen binding constructs to target molecules |
| WO2018147960A1 (en) | 2017-02-08 | 2018-08-16 | Imaginab, Inc. | Extension sequences for diabodies |
| KR20240059648A (ko) | 2017-04-19 | 2024-05-07 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 조작된 항원 수용체를 발현하는 면역 세포 |
| WO2019165121A1 (en) | 2018-02-21 | 2019-08-29 | Board Of Regents, The University Of Texas System | Methods for activation and expansion of natural killer cells and uses therof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1311829A (en) * | 1971-02-20 | 1973-03-28 | Hayashibara Co | Sealsoning of comestibles |
| US4945050A (en) * | 1984-11-13 | 1990-07-31 | Cornell Research Foundation, Inc. | Method for transporting substances into living cells and tissues and apparatus therefor |
| US5177011A (en) * | 1988-08-18 | 1993-01-05 | Calgene, Inc. | Plant elongation factor promoters, coding sequences and uses |
| JP2944721B2 (ja) * | 1990-08-22 | 1999-09-06 | 生化学工業株式会社 | エンドトキシンの測定剤 |
| NZ240921A (en) * | 1990-12-12 | 1994-06-27 | Zymogenetics Inc | G protein coupled glutamate receptor (neurotransmitters), recombinant production |
| KR100251995B1 (ko) * | 1991-08-23 | 2000-06-01 | 젠센 제임스 유. | 칼슘 수용체 활성 분자 |
| EP1466888A1 (en) * | 1991-08-23 | 2004-10-13 | Nps Pharmaceuticals, Inc. | Calcium receptor-active arylalkyl amines |
| IL105587A0 (en) * | 1992-05-08 | 1993-09-22 | Lilly Co Eli | Human metabotropic glutamate receptor and related dna compounds |
| CA2135646A1 (en) * | 1992-05-11 | 1993-11-25 | Kenneth G. Draper | Method and reagent for inhibiting viral replication |
| FI961251A0 (fi) * | 1993-09-20 | 1996-03-18 | Ciba Geigy | Ihmisten metabotrooppiset glutamaattireseptorialatyypit(HMR4, HMR6, HMR7)ja niihin liittyvät DNA-yhdisteet |
| US6274330B1 (en) * | 1993-12-30 | 2001-08-14 | Zymogenetics, Inc. | L-AP4 sensitive glutamate receptors |
| AU6912594A (en) * | 1994-05-16 | 1995-12-05 | Human Genome Sciences, Inc. | Neurotransmitter transporter |
| CA2200606A1 (en) * | 1995-07-26 | 1997-02-13 | Nps Pharmaceuticals, Inc. | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors and the use of such compounds in the treatment of neurological disorders and diseases |
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- 1997-02-20 EP EP97933988A patent/EP0882065B1/en not_active Expired - Lifetime
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008516606A (ja) * | 2004-10-14 | 2008-05-22 | カーネギー インスチチューション オブ ワシントン | 神経伝達物質センサーおよびそれを用いる方法 |
| JP2013059335A (ja) * | 2004-10-14 | 2013-04-04 | Carnegie Institution Of Washington | 神経伝達物質センサーおよびそれを用いる方法 |
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| IL125711A0 (en) | 1999-04-11 |
| EP0882065B1 (en) | 2007-08-08 |
| WO1997048724A3 (en) | 1998-03-26 |
| AU3715697A (en) | 1998-01-07 |
| EP0882065A2 (en) | 1998-12-09 |
| CA2246751A1 (en) | 1997-12-24 |
| DE69737990D1 (de) | 2007-09-20 |
| US6051688A (en) | 2000-04-18 |
| ATE369385T1 (de) | 2007-08-15 |
| AU719841B2 (en) | 2000-05-18 |
| WO1997048724A2 (en) | 1997-12-24 |
| US6084084A (en) | 2000-07-04 |
| IL125711A (en) | 2006-09-05 |
| DE69737990T2 (de) | 2008-09-11 |
| US6077675A (en) | 2000-06-20 |
| ES2292193T3 (es) | 2008-03-01 |
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