公开(公告)号：US06670167B1

公开(公告)日：2003-12-30

申请号：US09460421

申请日：1999-12-14

申请人： Ping Chen ,  Mark Anderson ,  Ya-Li Deng ,  Smita Gaur ,  Chen Chen Kan ,  Chun Luo ,  Karen Lundgren ,  Stephen Margosiak ,  Binh Nguyen ,  Patrick O'Connor ,  James Register ,  Anna Tempczyk Russell ,  Jay Sarup

发明人： Ping Chen ,  Mark Anderson ,  Ya-Li Deng ,  Smita Gaur ,  Chen Chen Kan ,  Chun Luo ,  Karen Lundgren ,  Stephen Margosiak ,  Binh Nguyen ,  Patrick O'Connor ,  James Register ,  Anna Tempczyk Russell ,  Jay Sarup

IPC分类号： C07H2104

CPC分类号： C12N9/1205 ,  C12Q1/34

摘要： The present invention relates to the identification, isolation and purification of the catalytic domain of the human effector checkpoint protein kinase (hChk1). A 1.7Å crystal structure of the hChk1 kinase domain in the active conformation is reported herein. The kinase domain of hChk1 and its associated crystal structure is described for use in the discovery, identification and characterization of inhibitors of hChk1. This structure provides a three-dimensional description of the binding site of the hChk1 for structure-based design of small molecule inhibitors thereof as therapeutic agents. Inhibitors of hChk1 find utility in the treatment of hyperproliferative disorders such as HIV and cancer.

摘要翻译： 本发明涉及人类效应子检测点蛋白激酶（hChk1）的催化结构域的鉴定，分离和纯化。 本文报道了活性构象中hChk1激酶结构域的1.7Å晶体结构。 描述了hChk1的激酶结构域及其相关晶体结构，用于hChk1抑制剂的发现，鉴定和表征。 该结构提供了hChk1的结合位点的三维描述，用于其作为治疗剂的小分子抑制剂的基于结构的设计。 hChk1的抑制剂可用于治疗过度增生性疾病如艾滋病毒和癌症。