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1. 发明申请

US20080063601A1 Compositions and methods relating to polycystic kidney disease 审中-公开
标题翻译：与多囊肾病有关的组合物和方法
公开(公告)号：US20080063601A1
公开(公告)日：2008-03-13
申请号：US11716980
申请日：2007-03-12
申请人： Stefan Somlo , Craig Crews , Stephanie Quinn , Dayne Okuhara
发明人： Stefan Somlo , Craig Crews , Stephanie Quinn , Dayne Okuhara
IPC分类号： A61K31/58 , A61K49/00 , A61P13/12 , C07K7/08 , C12Q1/02
CPC分类号： G01N33/5041 , A61K31/00 , G01N33/6872 , G01N2333/705 , G01N2800/347
摘要： Described herein are therapeutic strategies (methods and compositions) useful for treating conditions in which cilia are affected and which manifest with cysts and/or fibrosis, such as conditions in which the kidney, pancreas, liver and/or spleen are affected and contain cysts. Particular embodiments described herein are therapeutic strategies in which PC-2 agonists, particularly agonists (calcium channel agonists) that target PC-2 directly and/or selectively, are administered to individuals with mutations in PKD1, in order to alter the course of polycystic kidney disease, particularly ADPKD. In specific embodiments, the invention relates to use of PC-2 agonists triptolide and triptolide derivatives to regulate calcium release. In other aspects, the invention relates to use of PC-2 agonists to treat or aid in the treatment of any condition in which a calcium channel, such as the gene product of PKD1 and/or PKD2, is mutated; calcium signaling is abnormal; or both.
摘要翻译：本文描述了治疗策略（方法和组合物），其可用于治疗其中纤毛受到影响并且表现为囊肿和/或纤维化的病症的病症，例如肾脏，胰腺，肝脏和/或脾脏受影响并含有囊肿的病症。本文描述的具体实施方案是其中将靶向PC-2直接和/或选择性的PC-2激动剂，特别是激动剂（钙通道激动剂）施用于具有PKD1突变的个体的治疗策略，以便改变多囊肾的过程疾病，特别是ADPKD。在具体实施方案中，本发明涉及PC-2激动剂雷公藤内酯和雷公藤内酯衍生物调节钙释放的用途。在其它方面，本发明涉及PC-2激动剂用于治疗或辅助治疗其中钙通道（例如PKD1和/或PKD2的基因产物）突变的任何病症的用途; 钙信号异常; 或两者。

2. 发明授权

US07041298B2 Proteolysis targeting chimeric pharmaceutical 失效
公开(公告)号：US07041298B2
公开(公告)日：2006-05-09
申请号：US09953473
申请日：2001-09-10
申请人： Raymond J. Deshaies , Craig Crews , Kathleen M. Sakamoto
发明人： Raymond J. Deshaies , Craig Crews , Kathleen M. Sakamoto
IPC分类号： A61K39/385
CPC分类号： G01N33/5041 , C07K14/4703 , C07K2319/00 , C12N9/48 , C12P21/06 , C12Y304/11018 , G01N33/5008
摘要： The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains an ubiquitin pathway protein binding moiety which recognizes an ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains an ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.

3. 发明申请

US20080090785A1 Compounds For Enzyme Inhibition 有权
标题翻译：化合物用于酶抑制
公开(公告)号：US20080090785A1
公开(公告)日：2008-04-17
申请号：US11596028
申请日：2005-05-09
申请人： Mark Smyth , Guy Laidig , Ronald Borchardt , Barry Bunin , Craig Crews , John Musser , Kevin Shenk , Peggy Radel
发明人： Mark Smyth , Guy Laidig , Ronald Borchardt , Barry Bunin , Craig Crews , John Musser , Kevin Shenk , Peggy Radel
IPC分类号： A61K31/665 , A61K31/336 , A61K31/381 , A61K31/4523 , A61K31/4535 , A61P25/00 , A61P31/18 , C07D241/14 , C07D303/36 , C07D409/14 , C07D409/12 , C07D403/12 , C07D401/12 , C07D325/00 , C07D265/30 , A61P35/00 , A61P29/00 , A61P21/00 , A61K31/496 , A61K31/497 , A61K31/5355
CPC分类号： C07K5/0812 , C07K5/06034 , C07K5/0827 , Y02A50/412
摘要： Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsinlike activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.
摘要翻译：包括含杂原子的三元环的基于肽的化合物有效地选择性地抑制N末端亲核试剂（Ntn）水解酶的比活性。具有多种活性的那些Ntn的活性可被所描述的化合物差别地抑制。例如，本发明化合物可以选择性地抑制20S蛋白酶体的胰凝乳蛋白酶样活性。肽类化合物包括环氧化物或氮丙啶，并且在N-末端官能化。除了其他治疗用途之外，预期基于肽的化合物显示抗炎性质和抑制细胞增殖。

4. 发明申请

US20070191284A1 Compounds for enzyme inhibition 有权
公开(公告)号：US20070191284A1
公开(公告)日：2007-08-16
申请号：US11786217
申请日：2007-04-11
申请人： Mark Smyth , Guy Laidig , Ronald Borchardt , Barry Bunin , Craig Crews , John Musser
发明人： Mark Smyth , Guy Laidig , Ronald Borchardt , Barry Bunin , Craig Crews , John Musser
IPC分类号： A61K38/04 , C07K5/04
CPC分类号： C07K5/1016 , A61K38/00 , A61K38/07 , C07K5/0812 , C07K5/1008 , C07K5/1024
摘要： Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

5. 发明授权

US07208157B2 Proteolysis targeting chimeric pharmaceutical 有权
标题翻译：蛋白水解靶向嵌合药物
公开(公告)号：US07208157B2
公开(公告)日：2007-04-24
申请号：US10299203
申请日：2002-11-18
申请人： Raymond J. Dashaies , Craig Crews , Kathleen M. Sakamoto
发明人： Raymond J. Dashaies , Craig Crews , Kathleen M. Sakamoto
IPC分类号： A61K39/385
CPC分类号： C12N9/48 , C07K14/4703 , C07K2319/00 , C12P21/06 , C12Y304/11018 , G01N33/5008
摘要： The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains a ubiquitin pathway protein binding moiety which recognizes a ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains a ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.
摘要翻译：本发明基于提供靶向泛素化的组合物的发现。具体地，该组合物含有泛素途径蛋白结合部分，其识别泛素途径蛋白和识别靶蛋白的靶向部分。此外，本发明提供组合物文库，其中每种组合物含有泛素途径蛋白结合部分和分子文库的成员。本发明的文库可用于鉴定参与细胞的预定功能的蛋白质。

6. 发明申请

US20050245435A1 Compounds for enzyme inhibition 有权
标题翻译：用于酶抑制的化合物
公开(公告)号：US20050245435A1
公开(公告)日：2005-11-03
申请号：US11106879
申请日：2005-04-14
申请人： Mark Smyth , Guy Laidig , Ronald Borchardt , Barry Bunin , Craig Crews , John Musser , John Schneekloth , John Chabala
发明人： Mark Smyth , Guy Laidig , Ronald Borchardt , Barry Bunin , Craig Crews , John Musser , John Schneekloth , John Chabala
IPC分类号： A61K38/00 , A61K38/04 , C07K5/04 , C07K5/087
CPC分类号： C07K5/1016 , A61K38/00 , A61K38/07 , C07K5/0812 , C07K5/1008 , C07K5/1024
摘要： Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.
摘要翻译：包括含杂原子的三元环的基于肽的化合物有效地选择性地抑制N末端亲核试剂（Ntn）水解酶的比活性。具有多种活性的那些Ntn的活性可被所描述的化合物差别地抑制。例如，本发明化合物可以选择性地抑制20S蛋白酶体的胰凝乳蛋白酶样活性。基于肽的化合物包括至少三个肽单元，环氧化物或氮丙啶，并且在N-末端官能化。除了其他治疗用途之外，预期基于肽的化合物显示抗炎性质和抑制细胞增殖。

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