-
公开(公告)号：US20140179593A1
公开(公告)日：2014-06-26
申请号：US14118132
申请日：2012-05-16
IPC分类号： C07K14/47 , G01N33/566
CPC分类号： C07K14/47 , A61K38/00 , C07K2299/00 , C12N9/93 , C12Y603/02019 , G01N33/566 , G01N33/573 , G01N2333/9015 , G01N2440/36 , G01N2500/04
摘要： Provided herein is a novel binding pocket within NEDD8 co-E3 proteins that binds NEDD8 E2 enzymes. Particularly at its M-Terminus. Methods are provided for screening for compounds that bind to the disclosed E2-binding pocket in NEDD8 co-E3 proteins. Compounds that bind to the E2-binding pocket and optionally inhibit the activity of NEDD8 co-E3 proteins and pharmaceutical compositions comprising the same are further provided. The NEDD8 co-E3 inhibitors find use, as agents preventing the NEDDylation of a target protein, in inhibiting cell growth and methods for treating cancers, inflammatory disorders, and pathogenic infections. The preferred inhibitors are peptides corresponding to a M-terminal fragment of Dnc1, e.g. MTLASKLKRDD, MLKLRQLQKKKQ, and MIKLFSLKQQKK, which are substituted at the M-Terminus with an uncharged group (e.g. acyl).
摘要翻译： 本文提供了结合NEDD8 E2酶的NEDD8 co-E3蛋白内的新结合口袋。 特别是在其M-Terminus。 提供了用于筛选与NEDD8共-E3蛋白中公开的E2结合口袋结合的化合物的方法。 还提供结合E2结合口袋并任选地抑制NEDD8共-E3蛋白的活性的化合物和包含其的药物组合物。 NEDD8 co-E3抑制剂用作抑制靶蛋白的NEDD化作为抑制细胞生长的药剂以及用于治疗癌症，炎性疾病和致病性感染的方法。 优选的抑制剂是对应于Dnc1的M末端片段的肽，例如 MTLASKLKRDD，MLKLRQLQKKKQ和MIKLFSLKQQKK，它们在不带电荷的基团（例如酰基）的M-Terminus取代。
-
公开(公告)号：US09447156B2
公开(公告)日：2016-09-20
申请号：US14118132
申请日：2012-05-16
IPC分类号： G01N33/53 , C12N9/99 , C12N5/00 , C12N5/02 , A61K38/00 , C07K5/00 , C07K7/00 , C07K16/00 , C07K17/00 , C07K14/47 , C12N9/00 , G01N33/573 , G01N33/566
CPC分类号： C07K14/47 , A61K38/00 , C07K2299/00 , C12N9/93 , C12Y603/02019 , G01N33/566 , G01N33/573 , G01N2333/9015 , G01N2440/36 , G01N2500/04
摘要： Provided herein is a novel binding pocket within NEDD8 co-E3 proteins that binds NEDD8 E2 enzymes. Particularly at its M-Terminus. Methods are provided for screening for compounds that bind to the disclosed E2-binding pocket in NEDD8 co-E3 proteins. Compounds that bind to the E2-binding pocket and optionally inhibit the activity of NEDD8 co-E3 proteins and pharmaceutical compositions comprising the same are further provided. The NEDD8 co-E3 inhibitors find use, as agents preventing the NEDDylation of a target protein, in inhibiting cell growth and methods for treating cancers, inflammatory disorders, and pathogenic infections. The preferred inhibitors are peptides corresponding to a M-terminal fragment of Dnc1, e.g. MTLASKLKRDD, MLKLRQLQKKKQ, and MIKLFSLKQQKK, which are substituted at the M-Terminus with an uncharged group (e.g. acyl).
摘要翻译： 本文提供了结合NEDD8 E2酶的NEDD8 co-E3蛋白内的新结合口袋。 特别是在其M-Terminus。 提供了用于筛选与NEDD8共-E3蛋白中公开的E2结合口袋结合的化合物的方法。 还提供结合E2结合口袋并任选地抑制NEDD8共-E3蛋白的活性的化合物和包含其的药物组合物。 NEDD8 co-E3抑制剂用作抑制靶蛋白的NEDD化作为抑制细胞生长的药剂以及用于治疗癌症，炎性疾病和致病性感染的方法。 优选的抑制剂是对应于Dnc1的M末端片段的肽，例如 MTLASKLKRDD，MLKLRQLQKKKQ和MIKLFSLKQQKK，它们在不带电荷的基团（例如酰基）的M-Terminus取代。
-
搜索结果
2 条记录 (耗时 0.023 秒)