公开(公告)号：US20060149521A1

公开(公告)日：2006-07-06

申请号：US11274682

申请日：2005-11-14

申请人： John Baxter ,  Beatrice Darimont ,  Weijun Feng ,  Robert Fletterick ,  Peter Kushner ,  Richard Wagner ,  Brian West ,  Keith Yamamoto

发明人： John Baxter ,  Beatrice Darimont ,  Weijun Feng ,  Robert Fletterick ,  Peter Kushner ,  Richard Wagner ,  Brian West ,  Keith Yamamoto

IPC分类号： C07K14/72 ,  G06G7/48

CPC分类号： G01N33/6875 ,  G01N2500/20 ,  H01L21/3065 ,  H01L21/314 ,  H01L29/6659

摘要： The present invention comprises cocrystal of a nuclear receptor comprising a molecule bound to the coactivator binding site of said nuclear receptor. The present invention further comprises a machine-readable data storage medium encoded with machine readable data corresponding to the structure coordinates of amino acids of a nuclear receptor coactivator binding site which, when using a machine programmed with instructions for using said data, is capable of displaying a graphical three-dimensional representation of a molecular complex of a compound bound to a nuclear receptor coactivator binding site.

摘要翻译： 本发明包括核受体的共晶体，其包含与所述核受体的共激活因子结合位点结合的分子。 本发明还包括一种机器可读数据存储介质，其被编码有对应于核受体共激活剂结合位点的氨基酸的结构坐标的机读数据，当使用编程有用于使用所述数据的指令的机器时，能够显示 与核受体共激活子结合位点结合的化合物的分子复合物的图形三维表示。

公开(公告)号：US06965850B2

公开(公告)日：2005-11-15

申请号：US09281717

申请日：1999-03-30

申请人： John D. Baxter ,  Beatrice Darimont ,  Weijun Feng ,  Robert J. Fletterick ,  Peter J. Kushner ,  Richard L. Wagner ,  Brian L. West ,  Keith R. Yamamoto

发明人： John D. Baxter ,  Beatrice Darimont ,  Weijun Feng ,  Robert J. Fletterick ,  Peter J. Kushner ,  Richard L. Wagner ,  Brian L. West ,  Keith R. Yamamoto

IPC分类号： G01N33/53 ,  C07K14/47 ,  C07K14/705 ,  C12N15/09 ,  G01N33/00 ,  G01N33/15 ,  G01N33/50 ,  G01N33/68 ,  G06F17/30 ,  G06F17/50 ,  H01L21/3065 ,  H01L21/314 ,  H01L21/336 ,  G06N7/00 ,  G06G7/58

CPC分类号： H01L21/3065 ,  G01N33/6875 ,  G01N2500/20 ,  H01L21/314 ,  H01L29/6659

摘要： The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor coactivator binding. The invention includes a method for identifying residues comprising a coactivator binding site for a nuclear receptor of interest. Also included is a method of identifying agonists and/or antagonists that bind to a coactivator binding site of a nuclear receptor of interest. Agonists and antagonists of coactivator binding to nuclear receptors also are provided. The invention is exemplified by identification and manipulation of the coactivator binding site of the thyroid receptor (TR), and compounds that bind to this sites. The methods can be applied to other nuclear receptors including RAR, RXR, PPAR, VDR, ER, GR, PR, MR, and AR.

摘要翻译： 本发明涉及用于调节核受体共激活因子结合的方法和激动剂/拮抗剂化合物。 本发明包括用于鉴定残留物的方法，所述残基包含感兴趣的核受体的共激活子结合位点。 还包括鉴定结合感兴趣的核受体的共激活子结合位点的激动剂和/或拮抗剂的方法。 共激活剂与核受体结合的激动剂和拮抗剂也被提供。 本发明通过甲状腺受体（TR）的共激活因子结合位点的鉴定和操作以及与该位点结合的化合物来举例说明。 该方法可应用于其他核受体，包括RAR，RXR，PPAR，VDR，ER，GR，PR，MR和AR。