公开(公告)号：EP1012229A4

公开(公告)日：2004-04-07

申请号：EP98919854

申请日：1998-04-22

申请人： TULARIK INC

发明人： AMARAL M CATHERINE ,  CHEN JIN-LONG

IPC分类号： C12N15/09 ,  A61K48/00 ,  C07K14/47 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/85 ,  C12Q1/02 ,  C12Q1/68 ,  C12N1/00 ,  C12N15/11 ,  C12N15/63

CPC分类号： C12N15/85 ,  A61K48/00 ,  C07K14/4702 ,  C12N2830/00 ,  C12N2830/85

公开(公告)号：EP0861263A4

公开(公告)日：1999-09-29

申请号：EP96940512

申请日：1996-11-18

申请人： TULARIK INC

发明人： DE LA BROUSSE FABIENNE CHARLES ,  CHEN JIN-LONG

IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K14/575 ,  C12Q1/68 ,  C07H21/04

CPC分类号： C07K14/5759 ,  A61K38/00

公开(公告)号：EP1032834A4

公开(公告)日：2004-06-30

申请号：EP98960382

申请日：1998-11-20

申请人： TULARIK INC

发明人： LUSTIG KEVIN ,  BAEUERLE PATRICK ,  BECKMANN HOLGER ,  CHEN JIN-LONG ,  SHAN BEI

IPC分类号： G01N33/566 ,  G01N33/15 ,  G01N33/50 ,  G01N33/542 ,  G01N33/68 ,  G01N33/74 ,  C07K14/705

CPC分类号： G01N33/74 ,  G01N33/542 ,  G01N2333/575 ,  G01N2333/70567

摘要： Methods for identifying modulators of nuclear hormone receptor function comprise the steps of (a) forming a mixture comprising a nuclear hormone receptor, a peptide sensor and a candidate agent, but not a natural coactivator protein of the receptor, wherein the sensor provides direct, in vitro binding to the receptor under assay conditions; (b) measuring an agent-biased binding of the sensor to the receptor; and (c) comparing the agent-biased binding with a corresponding unbiased binding of the sensor to the receptor. In particular embodiments, the sensor comprises an amphipathic alpha helix nuclear hormone interacting domain comprising a recited nuclear hormone transcriptional coactivator motif sequence, the sensor is present at sub-micromolar concentration, the binding reaction occurs in solution, the sensor comprises a fluorescent label and the measuring step comprises detecting fluorescence polarization of the label. Reagents include labeled sensor peptides and reaction mixtures consisting essentially of nuclear hormone receptor, a peptide and a candidatent.

公开(公告)号：EP1027424A4

公开(公告)日：2004-04-07

申请号：EP98952232

申请日：1998-10-09

申请人： TULARIK INC

发明人： AMARAL M CATHERINE ,  ZHANG NING ,  CHEN JIN-LONG

IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K14/47 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12Q1/68 ,  C12N1/00 ,  C12N15/11 ,  C12N15/12 ,  C12N15/63 ,  C12Q1/02

CPC分类号： C12Q1/6897 ,  A61K38/00 ,  C07K14/4702

公开(公告)号：EP0929665A4

公开(公告)日：2003-03-12

申请号：EP97940763

申请日：1997-09-02

申请人： TULARIK INC

发明人： SHAN BEI ,  LEARNED R MARC ,  AMARAL M CATHERINE ,  MCKNIGHT STEVEN L ,  DE LA BROUSSE FABIENNE C ,  CHEN JIN-LONG

IPC分类号： C12N15/09 ,  C12N5/10 ,  C12Q1/66 ,  C12Q1/68 ,  G01N33/50 ,  C12N15/10 ,  C12N15/63 ,  C12N15/64 ,  C12N15/85

CPC分类号： G01N33/5023 ,  A01K2217/072 ,  C12N15/8509 ,  C12N2510/00 ,  C12N2830/008 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5044 ,  G01N2500/00

摘要： The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, as shown in the figure, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expressions levels indicates that the candidate agent modulates gene expression.