专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

1. 发明申请

WO2017053864A1 CYSTEINE PROTEASE INHIBITORS 审中-公开
标题翻译： CYSTEINE PROTEASE抑制剂
公开(公告)号：WO2017053864A1
公开(公告)日：2017-03-30
申请号：PCT/US2016/053539
申请日：2016-09-23
申请人： INTRACELLULAR TECHNOLOGIES, LLC , PHELPS, David , JOHNSON, Gary , BARTIK, Mary, Margaret , BENSEN, Eric, S. , HALVERSON, David, J. , BOGYO, Matthew, S.
发明人： PHELPS, David , JOHNSON, Gary , BARTIK, Mary, Margaret , BENSEN, Eric, S. , HALVERSON, David, J. , BOGYO, Matthew, S.
IPC分类号： C07K5/04 , C07K5/08
CPC分类号： C07K5/06052 , C07K5/0202 , C07K5/06026 , C07K5/06034 , C07K5/06104 , C07K5/06113 , C07K5/0812 , C07K5/0819 , C07K5/0821 , C07K5/101
摘要： The invention provides compounds and compositions that inhibit one or more cysteine proteases (e.g. caspases or cysteine cathepsins), as well as kits comprising such compounds and compositions. The invention also provides therapeutic methods and screening methods that utilize such compounds and compositions.
摘要翻译：本发明提供抑制一种或多种半胱氨酸蛋白酶（例如胱天蛋白酶或半胱氨酸组织蛋白酶）的化合物和组合物，以及包含这些化合物和组合物的试剂盒。本发明还提供了利用这些化合物和组合物的治疗方法和筛选方法。

2. 发明申请

WO2012118715A3 NON-PEPTIDIC QUENCHED FLUORESCENT IMAGING PROBES 审中-公开
标题翻译：非磷酸荧光成像探针
公开(公告)号：WO2012118715A3
公开(公告)日：2012-11-01
申请号：PCT/US2012026601
申请日：2012-02-24
申请人： UNIV LELAND STANFORD JUNIOR , BOGYO MATTHEW S , EDGINGTON LAURA E , VERDOES MARTIJN
发明人： BOGYO MATTHEW S , EDGINGTON LAURA E , VERDOES MARTIJN
IPC分类号： C07D249/04 , A61K49/10 , C07D403/12 , C07D409/12 , C07D413/12
CPC分类号： A61K49/0052 , A61K49/0021 , A61K49/0032 , C07D249/04 , C07D409/12 , C07D409/14 , C07F5/022
摘要： Methods and materials for the imaging of cells and tissues containing active proteases such as cathepsin are disclosed. The present materials include activity based probes that bind to an enzyme and are subsequently cleaved. Cleavage results in covalent attachment of a fluorescent signal to a target protease due to removal of a quenching group which, when present on the probe causes altered or no fluorescence. The probes are non-peptidic, small molecule scaffolds linked to a reactive acyloxymethyl ketone group, a fluorophore and a quencher. The probes are cell permeable and may use, for example, a QSY21 (CAS 304014- 13-9) quencher and a cyanine dye. The probes form covalent bonds with the active site of cysteine cathepsins, proteases that are upregulated at the tumor boundaries with normal tissue and at sites of inflammation.
摘要翻译：公开了用于成像包含活性蛋白酶如组织蛋白酶的细胞和组织成像的方法和材料。本发明的材料包括与酶结合并随后被切割的基于活性的探针。切割导致荧光信号与靶蛋白酶共价连接，因为去除了淬灭基团，当淬灭基团存在于探针上时会导致改变或不发生荧光。探针是与反应性酰氧基甲基酮基，荧光团和猝灭剂连接的非肽，小分子支架。探针是细胞可渗透的，并且可以使用例如QSY21（CAS 304014-13-9）猝灭剂和花青染料。探针与半胱氨酸组织蛋白酶的活性位点形成共价键，在正常组织和炎症部位的肿瘤边界处上调蛋白酶。

3. 发明申请

WO2012118715A2 NON-PEPTIDIC QUENCHED FLUORESCENT IMAGING PROBES 审中-公开
标题翻译：非肽猝灭荧光成像探针
公开(公告)号：WO2012118715A2
公开(公告)日：2012-09-07
申请号：PCT/US2012/026601
申请日：2012-02-24
申请人： THE BOARD OF TRUSTEES OF LELAND STANFORD JUNIOR UNIVERSITY , BOGYO, Matthew, S. , EDGINGTON, Laura, E. , VERDOES, Martijn
发明人： BOGYO, Matthew, S. , EDGINGTON, Laura, E. , VERDOES, Martijn
IPC分类号： C07D249/04 , C07D409/12 , C07D403/12 , C07D413/12 , A61K49/10
CPC分类号： A61K49/0052 , A61K49/0021 , A61K49/0032 , C07D249/04 , C07D409/12 , C07D409/14 , C07F5/022
摘要： Methods and materials for the imaging of cells and tissues containing active proteases such as cathepsin are disclosed. The present materials include activity based probes that bind to an enzyme and are subsequently cleaved. Cleavage results in covalent attachment of a fluorescent signal to a target protease due to removal of a quenching group which, when present on the probe causes altered or no fluorescence. The probes are non-peptidic, small molecule scaffolds linked to a reactive acyloxymethyl ketone group, a fluorophore and a quencher. The probes are cell permeable and may use, for example, a QSY21 (CAS 304014- 13-9) quencher and a cyanine dye. The probes form covalent bonds with the active site of cysteine cathepsins, proteases that are upregulated at the tumor boundaries with normal tissue and at sites of inflammation.
摘要翻译：公开了用于成像含有活性蛋白酶如组织蛋白酶的细胞和组织的方法和材料。本发明材料包括与酶结合并随后被切割的基于活性的探针。裂解导致荧光信号与目标蛋白酶的共价连接，因为除去了淬灭基团，当探针上存在引起改变的荧光或无荧光时。探针是与活性酰氧基甲基酮基团，荧光团和猝灭剂连接的非肽类小分子支架。探针是可渗透细胞的，可以使用例如QSY21（CAS 304014-13-9）淬灭剂和花青染料。探针与半胱氨酸组织蛋白酶的活性位点形成共价键，蛋白酶在与正常组织和炎症部位的肿瘤边界上调。

4. 发明申请

WO2008094205A2 A MILD CHEMICALLY CLEAVABLE LINKER SYSTEM 审中-公开
标题翻译：一种化学可清除的连接器系统
公开(公告)号：WO2008094205A2
公开(公告)日：2008-08-07
申请号：PCT/US2007/017233
申请日：2007-08-01
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , BOGYO, Matthew, S. , VERHELST, Stephen, H., L. , FONOVIC, Marko
发明人： BOGYO, Matthew, S. , VERHELST, Stephen, H., L. , FONOVIC, Marko
CPC分类号： G01N33/54353 , C07C271/20 , C07C2603/18 , C07D495/04 , C07K1/13
摘要： A linker system is provided where a small molecule reactive group, e.g., an activity based probe which binds to certain enzymes at the active site, is linked through an aryl diazo linker to an affinity molecule such as biotin. The reactive group may comprise a number of functionalities known to react with a specific target to be studied. This enables the probe to be exposed to analytes, such as proteins and bind specifically to them to form a complex having an affinity molecule allowing immobilization of the bound analyte on an affinity column or other support, e.g. with streptavidin. Then, the linker is cleaved without causing removal of the affinity group or dissociation of the probe from the analyte. The linker is cleaved under mild reducing conditions, e.g., dithionite. The probe is synthesized along with the linker on a solid support.
摘要翻译：提供了一种接头系统，其中将小分子反应性基团例如与活性位点上的某些酶结合的基于活性的探针通过芳基重氮接头连接到亲和分子例如生物素。反应性基团可以包括已知与待研究的特定靶标反应的许多官能团。这使得探针能够暴露于分析物，例如蛋白质，并且特异性地与其结合，形成具有允许将结合的分析物固定在亲和柱或其它载体上的亲和分子的复合物，例如。与链霉亲和素。然后，将接头切割而不引起亲和基团的去除或探针与分析物的解离。接头在温和的还原条件下裂解，例如连二亚硫酸盐。该探针与固体支持物上的接头一起合成。

5. 发明申请

WO2008042480A3 EPOXIDE INHIBITORS OF CYSTEINE PROTEASES 审中-公开
公开(公告)号：WO2008042480A3
公开(公告)日：2008-04-10
申请号：PCT/US2007/071145
申请日：2007-06-13
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , BOGYO, Matthew S. , SADAGHIANI, Amir M. , VERHELST, Steven
发明人： BOGYO, Matthew S. , SADAGHIANI, Amir M. , VERHELST, Steven
IPC分类号： A61K31/335 , A01N43/20 , A01N43/24
摘要： Provided herein are novel epoxide inhibitors of cysteine proteases, compositions comprising the epoxide inhibitors, and packaged pharmaceuticals. Also provided are methods of inhibiting a papain-family cysteine protease and methods of treating or preventing a disease by administering a composition containing an epoxide inhibitor of the invention. The compositions may be administered in combination with another therapeutic agent.

6. 发明申请

WO2008042480A2 EPOXIDE INHIBITORS OF CYSTEINE PROTEASES 审中-公开
标题翻译：环氧化酶抑制剂CYSTEINE PROTEASES
公开(公告)号：WO2008042480A2
公开(公告)日：2008-04-10
申请号：PCT/US2007071145
申请日：2007-06-13
申请人： UNIV LELAND STANFORD JUNIOR , BOGYO MATTHEW S , SADAGHIANI AMIR M , VERHELST STEVEN
发明人： BOGYO MATTHEW S , SADAGHIANI AMIR M , VERHELST STEVEN
IPC分类号： A61K31/5377
CPC分类号： C07D401/12 , C07D303/48
摘要： Provided herein are novel epoxide inhibitors of cysteine proteases, compositions comprising the epoxide inhibitors, and packaged pharmaceuticals. Also provided are methods of inhibiting a papain-family cysteine protease and methods of treating or preventing a disease by administering a composition containing an epoxide inhibitor of the invention. The compositions may be administered in combination with another therapeutic agent.
摘要翻译：本文提供了半胱氨酸蛋白酶的新型环氧化物抑制剂，包含环氧化物抑制剂和包装药物的组合物。还提供了通过施用含有本发明的环氧化物抑制剂的组合物来抑制木瓜蛋白酶家族半胱氨酸蛋白酶的方法和治疗或预防疾病的方法。组合物可以与另一种治疗剂组合施用。

7. 发明申请

WO2012118715A9 NON-PEPTIDIC QUENCHED FLUORESCENT IMAGING PROBES 审中-公开
标题翻译：非磷酸荧光成像探针
公开(公告)号：WO2012118715A9
公开(公告)日：2013-02-21
申请号：PCT/US2012026601
申请日：2012-02-24
申请人： UNIV LELAND STANFORD JUNIOR , BOGYO MATTHEW S , EDGINGTON LAURA E , VERDOES MARTIJN
发明人： BOGYO MATTHEW S , EDGINGTON LAURA E , VERDOES MARTIJN
IPC分类号： C07D249/04 , A61K49/10 , C07D403/12 , C07D409/12 , C07D413/12
CPC分类号： A61K49/0052 , A61K49/0021 , A61K49/0032 , C07D249/04 , C07D409/12 , C07D409/14 , C07F5/022
摘要： Methods and materials for the imaging of cells and tissues containing active proteases such as cathepsin are disclosed. The present materials include activity based probes that bind to an enzyme and are subsequently cleaved. Cleavage results in covalent attachment of a fluorescent signal to a target protease due to removal of a quenching group which, when present on the probe causes altered or no fluorescence. The probes are non-peptidic, small molecule scaffolds linked to a reactive acyloxymethyl ketone group, a fluorophore and a quencher. The probes are cell permeable and may use, for example, a QSY21 (CAS 304014- 13-9) quencher and a cyanine dye. The probes form covalent bonds with the active site of cysteine cathepsins, proteases that are upregulated at the tumor boundaries with normal tissue and at sites of inflammation.
摘要翻译：公开了用于成像包含活性蛋白酶如组织蛋白酶的细胞和组织成像的方法和材料。本发明的材料包括与酶结合并随后被切割的基于活性的探针。切割导致荧光信号与靶蛋白酶共价连接，因为去除了淬灭基团，当淬灭基团存在于探针上时会导致改变或不发生荧光。探针是与反应性酰氧基甲基酮基，荧光团和猝灭剂连接的非肽，小分子支架。探针是细胞可渗透的，并且可以使用例如QSY21（CAS 304014-13-9）猝灭剂和花青染料。探针与半胱氨酸组织蛋白酶的活性位点形成共价键，在正常组织和炎症部位的肿瘤边界处上调蛋白酶。

8. 发明申请

WO2011075678A1 SPECIFIC INHIBITORS AND ACTIVE SITE PROBES FOR LEGUMAIN 审中-公开
标题翻译：特殊抑制剂和主动现场探测器
公开(公告)号：WO2011075678A1
公开(公告)日：2011-06-23
申请号：PCT/US2010/061109
申请日：2010-12-17
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , LEE, Jiyoun , YIN, Fangfang , BOGYO, Matthew, S. , EDGINGTON, Laura
发明人： LEE, Jiyoun , YIN, Fangfang , BOGYO, Matthew, S. , EDGINGTON, Laura
IPC分类号： A61K38/48 , A61K38/06
CPC分类号： A61K49/0056 , A61K49/0032 , A61K49/0052 , C07K5/06078 , C07K5/06086 , C07K5/06139
摘要： Compounds which specifically inhibit legumain, also known as asparaginyl endopeptidase are provided. The compounds have an epoxide or N-Michael acceptor warhead, and have an asparagine side chain attached to a nitrogen atom in the backbone adjacent the warhead. The compounds also preferably comprise a proline residue adjacent the asparagine, and the compound may also contain a third residue and/or a label for cellular or in vivo imaging of active legumain.
摘要翻译：提供了特异性抑制豆腐素的化合物，也被称为天冬酰胺酰肽内肽酶。这些化合物具有环氧化物或N-Michael受体弹头，并且在邻近弹头的骨架中具有连接到骨架上的氮原子的天冬酰胺侧链。所述化合物还优选包含邻近天冬酰胺的脯氨酸残基，并且所述化合物还可以含有第三残基和/或用于活细胞瘤的细胞或体内成像的标记。

9. 发明申请

WO2008094205A3 A MILD CHEMICALLY CLEAVABLE LINKER SYSTEM 审中-公开
标题翻译：轻度化学可切割链接器系统
公开(公告)号：WO2008094205A3
公开(公告)日：2008-11-06
申请号：PCT/US2007017233
申请日：2007-08-01
申请人： UNIV LELAND STANFORD JUNIOR , BOGYO MATTHEW S , VERHELST STEPHEN H L , FONOVIC MARKO
发明人： BOGYO MATTHEW S , VERHELST STEPHEN H L , FONOVIC MARKO
IPC分类号： C12Q1/00 , G01N33/00
CPC分类号： G01N33/54353 , C07C271/20 , C07C2603/18 , C07D495/04 , C07K1/13
摘要： A linker system is provided where a small molecule reactive group, e.g., an activity based probe which binds to certain enzymes at the active site, is linked through an aryl diazo linker to an affinity molecule such as biotin. The reactive group may comprise a number of functionalities known to react with a specific target to be studied. This enables the probe to be exposed to analytes, such as proteins and bind specifically to them to form a complex having an affinity molecule allowing immobilization of the bound analyte on an affinity column or other support, e.g. with streptavidin. Then, the linker is cleaved without causing removal of the affinity group or dissociation of the probe from the analyte. The linker is cleaved under mild reducing conditions, e.g., dithionite. The probe is synthesized along with the linker on a solid support.
摘要翻译：提供了连接子系统，其中小分子反应基团，例如与活性位点上的某些酶结合的基于活性的探针，通过芳基重氮连接子与亲和分子如生物素连接。反应基团可以包含许多已知与待研究的特定靶标反应的官能团。这使得探针暴露于分析物例如蛋白质并且与它们特异性结合以形成具有亲和分子的复合物，从而允许将结合的分析物固定在亲和柱或其他支持物上，与链霉抗生物素蛋白。然后，接头被切割而不引起亲和基团或探针与分析物的解离。接头在温和还原条件下裂解，例如连二亚硫酸盐。探针在固体支持物上与连接物一起合成。

10. 发明申请

WO2009124265A1 PROBES FOR IN VIVO TARGETING OF ACTIVE CYSTEINE PROTEASES 审中-公开
标题翻译：针对活性CYSTEINE蛋白的体外检测
公开(公告)号：WO2009124265A1
公开(公告)日：2009-10-08
申请号：PCT/US2009/039496
申请日：2009-04-03
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , BOGYO, Matthew, S. , BLUM, Galia , BERGER, Alicia, B. , CHENG, Zhen , GAMBHIR, Sanjiv, S.
发明人： BOGYO, Matthew, S. , BLUM, Galia , BERGER, Alicia, B. , CHENG, Zhen , GAMBHIR, Sanjiv, S.
IPC分类号： A61B6/00 , G01N33/48
CPC分类号： A61K51/08 , A61B6/508 , A61K49/0032 , A61K49/0056 , A61K51/0495 , A61K51/088
摘要： Activity-based probes, which are specific for certain active cysteine proteases (caspase, cathepsin and legumain) and carry radioactive labels, are disclosed. The present probes comprise an acyloxymethyketone (AOMK) "warhead" that binds only to active enzyme. The probes further comprise peptide-like structure that targets the probe to a specific cysteine protease or protease family, and a radiolabel on the probe, which is bound to the targeted enzyme. It has been found that the present probes are stable in vivo and give specific target images distinguishable over background. The preferred probes are labeled with a positron-emitting agent such as 64 Cu, 125 I (SPECT) and 99m Tc (PET). The probes show in vivo half-life and stability well suited for imaging.
摘要翻译：公开了基于活性的探针，其特异于某些活性半胱氨酸蛋白酶（半胱天冬酶，组织蛋白酶和legumain）和携带放射性标记。本发明的探针包括只与活性酶结合的酰氧基甲基酮（AOMK）“弹头”。探针进一步包含将探针靶向特定半胱氨酸蛋白酶或蛋白酶家族的肽样结构，以及与靶向酶结合的探针上的放射性标记。已经发现本发明的探针在体内是稳定的，并且可以在背景下区分特定的目标图像。优选的探针用正电子发射剂如64Cu，125I（SPECT）和99mTc（PET）标记。探针显示体内半衰期和稳定性，非常适合成像。

你已经成功收藏专利！

检索式保存成功!

IPRDB

热门服务

关于我们

友情链接

联系方式