公开(公告)号：US6100445A

公开(公告)日：2000-08-08

申请号：US954536

申请日：1997-10-20

申请人： Tara Seshadri ,  Ping Li ,  Hamish Allen ,  Subhashis Banerjee ,  Michael Paskind

发明人： Tara Seshadri ,  Ping Li ,  Hamish Allen ,  Subhashis Banerjee ,  Michael Paskind

IPC分类号： A01K67/027 ,  C12N5/10 ,  C12N9/64 ,  C12N15/09 ,  C12N15/57 ,  C12N15/85 ,  C12P21/00 ,  C12Q1/37 ,  G01N33/15 ,  C12N5/00 ,  C07H21/04 ,  C12N15/00

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  C12N9/6475 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03

摘要： A transgenic mouse having somatic and germ cells in which at least one allele of an endogenous interleukin-1.beta. converting enzyme (ICE) gene is functionally disrupted is provided. The mouse may be heterozygous or, more preferably, homozygous for the ICE gene disruption. In homozygous mice, secretion of mature interleukin-1.beta. and interleukin-1.alpha. is substantially reduced relative to non-mutant mice. The mice of the invention can be used as positive controls to evaluate the efficacy of ICE inhibitors and to identify disease conditions that can be treated with ICE inhibitors. A transgenic mouse having functionally disrupted endogenous ICE genes but which has been reconstituted with a human ICE gene is also provided. This mouse can be used to identify agents that inhibit human ICE in vivo. Nucleic acid constructs for functionally disrupting an endogenous ICE gene in a host cell, recombinant vectors including the nucleic acid construct, and host cells into which the nucleic acid construct has been introduced are also encompassed by the invention.

摘要翻译： 提供具有体内和生殖细胞的转基因小鼠，其中内源性白细胞介素-1β转换酶（ICE）基因的至少一个等位基因被功能性地破坏。 对于ICE基因破坏，小鼠可以是杂合的，或者更优选地是纯合的。 在纯合小鼠中，相对于非突变小鼠，成熟白细胞介素-1β和白细胞介素-1α的分泌显着降低。 本发明的小鼠可用作阳性对照以评估ICE抑制剂的功效并鉴定可用ICE抑制剂治疗的疾病状况。 还提供了具有功能性破坏内源性ICE基因但已经用人ICE基因重构的转基因小鼠。 该小鼠可用于鉴别体内抑制人类ICE的药物。 用于功能性破坏宿主细胞内的内源性ICE基因的核酸构建物，包括核酸构建体的重组载体和已经导入了核酸构建体的宿主细胞也包括在本发明中。

公开(公告)号：US20060074102A1

公开(公告)日：2006-04-06

申请号：US11129624

申请日：2005-05-13

申请人： Kevin Cusack ,  Jose-Andres Salmeron-Garcia ,  Thomas Gordon ,  Claude Barberis ,  Hamish Allen ,  Agniezka Bischoff ,  Anna Ericsson ,  Michael Friedman ,  Dawn George ,  Gregory Roth ,  Robert Talanian ,  Christine Thomas ,  Grier Wallace ,  Neil Wishart ,  Zhengtian Yu

发明人： Kevin Cusack ,  Jose-Andres Salmeron-Garcia ,  Thomas Gordon ,  Claude Barberis ,  Hamish Allen ,  Agniezka Bischoff ,  Anna Ericsson ,  Michael Friedman ,  Dawn George ,  Gregory Roth ,  Robert Talanian ,  Christine Thomas ,  Grier Wallace ,  Neil Wishart ,  Zhengtian Yu

IPC分类号： A61K31/4743 ,  C07D498/02

CPC分类号： C07D471/04 ,  A61K31/4743 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04 ,  Y02A50/481

摘要： A compound or pharmaceutically acceptable salts thereof of Formula (I) wherein the substituents are as defined herein, which are useful as kinase inhibitors.

摘要翻译： 式（I）的化合物或其药学上可接受的盐，其中取代基如本文所定义，其可用作激酶抑制剂。