CN101107529A - G蛋白偶联受体 - Google Patents

G蛋白偶联受体 Download PDF

Info

Publication number: CN101107529A
Authority: CN; China
Prior art keywords: gpr39; leu; ser; seq; val
Prior art date: 2004-12-01
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

Application number

CNA2005800471189A

Other languages

English (en)

Chinese (zh)

Inventor

D·W·E·莫查尔斯

B·C·J·-C·莫罗克斯

T·L·H·皮特斯

I·I·T·德波特尔

B·考利

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Janssen Pharmaceutica NV

Original Assignee

Janssen Pharmaceutica NV

Priority date (The priority date 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 date listed.)

2004-12-01

Filing date

2005-11-30

Publication date

2008-01-16

2005-11-30 Application filed by Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV

2008-01-16 Publication of CN101107529A publication Critical patent/CN101107529A/zh

Status Pending legal-status Critical Current

Links

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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere

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Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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CNA2005800471189A 2004-12-01 2005-11-30 G蛋白偶联受体 Pending CN101107529A (zh)

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JP (1)	JP2008521419A (ko)
KR (1)	KR20070086003A (ko)
CN (1)	CN101107529A (ko)
AU (1)	AU2005311321A1 (ko)
CA (1)	CA2587534A1 (ko)
NO (1)	NO20073294L (ko)
RU (1)	RU2007124609A (ko)
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CN111443209A (zh) *	2020-03-26	2020-07-24	中国中医科学院医学实验中心	一种筛选非激动剂型PPARγ配体的方法

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WO2005103283A1 (ja) *	2004-04-23	2005-11-03	Takeda Pharmaceutical Company Limited	新規スクリーニング方法
CN101467047A (zh) *	2006-06-08	2009-06-24	詹森药业有限公司	G蛋白偶联受体39

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EP1280937A2 (en) *	2000-04-26	2003-02-05	Millennium Pharmaceuticals, Inc.	Methods and compositions for the diagnosis and treatment of cardiovascular and tumorigenic disease using 4941
WO2002086460A1 (en) *	2001-04-20	2002-10-31	Consensus Pharmaceuticals, Inc.	Methods for identifying ligands of g-protein-coupled receptors
US20030232769A1 (en) *	2002-06-17	2003-12-18	Isis Pharmaceuticals Inc.	Antisense modulation of G protein-coupled receptor 39 expression
CA2498264A1 (en) *	2002-09-09	2004-05-13	Nura, Inc.	G protein coupled receptors and uses thereof
US20040071708A1 (en) *	2002-09-26	2004-04-15	Immusol, Inc.	GPR 39 modulators that control cancerous cell growth
JP4733390B2 (ja) *	2002-10-31	2011-07-27	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	Ｃｎｓにおけるｃｒｈ応答性遺伝子
WO2004099782A2 (en) *	2003-05-05	2004-11-18	Bayer Healthcare Ag	Diagnostics and therapeutics for diseases associated with g-protein-coupled receptor gpr39 (gpr39)

2005
- 2005-11-30 CA CA002587534A patent/CA2587534A1/en not_active Abandoned
- 2005-11-30 RU RU2007124609/15A patent/RU2007124609A/ru not_active Application Discontinuation
- 2005-11-30 EP EP05817427A patent/EP1820026A1/en not_active Withdrawn
- 2005-11-30 AU AU2005311321A patent/AU2005311321A1/en not_active Abandoned
- 2005-11-30 JP JP2007543845A patent/JP2008521419A/ja active Pending
- 2005-11-30 CN CNA2005800471189A patent/CN101107529A/zh active Pending
- 2005-11-30 WO PCT/EP2005/056350 patent/WO2006058889A1/en active Application Filing
- 2005-11-30 KR KR1020077013092A patent/KR20070086003A/ko not_active Withdrawn
2007
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Cited By (2)

* Cited by examiner, † Cited by third party
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CN111443209A (zh) *	2020-03-26	2020-07-24	中国中医科学院医学实验中心	一种筛选非激动剂型PPARγ配体的方法
CN111443209B (zh) *	2020-03-26	2022-12-20	中国中医科学院医学实验中心	一种筛选非激动剂型PPARγ配体的方法

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KR20070086003A (ko)	2007-08-27
WO2006058889A1 (en)	2006-06-08
NO20073294L (no)	2007-08-29
EP1820026A1 (en)	2007-08-22
JP2008521419A (ja)	2008-06-26
CA2587534A1 (en)	2006-06-08
RU2007124609A (ru)	2009-01-10
ZA200704526B (en)	2008-11-26
AU2005311321A1 (en)	2006-06-08

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Smith et al.	1997	The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells
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