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公开(公告)号：WO2012012653A1
公开(公告)日：2012-01-26
申请号：PCT/US2011/044882
申请日：2011-07-21
申请人： ERRICO, Joseph P. , MUGRAGE, Benjamin , TURCHI, Ignatius , SILLS, Matthew , ONG, Jane , ALLOCCO, John , WINES, Pam , BASTOS, Margarita
发明人： ERRICO, Joseph P. , MUGRAGE, Benjamin , TURCHI, Ignatius , SILLS, Matthew , ONG, Jane , ALLOCCO, John , WINES, Pam , BASTOS, Margarita
IPC分类号： G01N33/574
CPC分类号： A61K31/517 , A61K31/4709 , A61K31/5377 , A61K45/06 , A61K2300/00
摘要： Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.
摘要翻译： 提供了通过施用p53和MDM2结合的抑制剂与EGFR抑制剂的组合来治疗受试者的增殖性疾病，病症或病症的方法。 与单独施用一种试剂相比，所公开方法的各种实施方案提供协同的抗增殖或抗凋亡作用。
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公开(公告)号：WO2011085129A3
公开(公告)日：2011-09-01
申请号：PCT/US2011020418
申请日：2011-01-06
申请人： ERRICO JOSEPH P , MUGRAGE BENJAMIN , TURCHI IGNATIUS , SILLS MATTHEW , HERRON JEFFREY D , LODATO NICHOLAS J , ONG JANE , PINE COREY , FEAVER WILLIAM J , ALLOCCO JOHN , WINES PAM
发明人： ERRICO JOSEPH P , MUGRAGE BENJAMIN , TURCHI IGNATIUS , SILLS MATTHEW , HERRON JEFFREY D , LODATO NICHOLAS J , ONG JANE , PINE COREY , FEAVER WILLIAM J , ALLOCCO JOHN , WINES PAM
IPC分类号： A61K31/535
CPC分类号： C07D215/26 , A61K31/47 , A61K31/4709 , A61K31/496 , A61K45/06 , C07C335/26 , C07D207/48 , C07D209/08 , C07D239/42 , C07D239/47 , C07D239/52 , C07D285/135 , C07D295/26 , C07D307/54 , C07D401/12 , C07D401/14 , C07D403/12 , C07D405/06 , C07D405/14 , C07D409/06 , C07D409/14 , C07D417/14 , G06F19/16
摘要： Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.
摘要翻译： 本文提供了具有抗增殖作用的化合物。 还提供了可以调节包含二聚化臂和结构域间连接臂（例如EGFR）的多结构域蛋白的活性的化合物，其中未束缚的延长构象是活性状态并且束缚构象是非活性状态，导致自我抑制构型 。 还提供了用于鉴定这些化合物的方法和药效团。 其他方面提供增殖性疾病，障碍或病症（例如与EGFR相关的那些）的方法或治疗性治疗。
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公开(公告)号：WO2011085126A3
公开(公告)日：2012-02-23
申请号：PCT/US2011020414
申请日：2011-01-06
申请人： ERRICO JOSEPH P , MUGRAGE BENJAMIN , TURCHI IGNATIUS , SILLS MATTHEW , ONG JANE , ALLOCCO JOHN , WINES PAM
发明人： ERRICO JOSEPH P , MUGRAGE BENJAMIN , TURCHI IGNATIUS , SILLS MATTHEW , ONG JANE , ALLOCCO JOHN , WINES PAM
IPC分类号： A61K31/555
CPC分类号： C07D215/26 , A61K31/47 , A61K31/4709 , A61K31/496 , A61K45/06 , C07C335/26 , C07D207/48 , C07D209/08 , C07D239/42 , C07D239/47 , C07D239/52 , C07D285/135 , C07D295/26 , C07D307/54 , C07D401/12 , C07D401/14 , C07D403/12 , C07D405/06 , C07D405/14 , C07D409/06 , C07D409/14 , C07D417/14 , G06F19/16
摘要： Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.
摘要翻译： 本文提供具有抗增殖作用的化合物。 还提供了可以调节包含二聚化臂和跨域系链例如EGFR的多结构域蛋白质的活性的化合物，其中无阻塞的扩展构象是活性状态，并且系留构象是无活性状态，导致自身抑制构型 。 还提供了用于鉴定这些化合物的方法和药效团。 其他方面为增殖性疾病，病症或病症（例如与EGFR相关的病症）提供方法或治疗方法。
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公开(公告)号：WO2011085129A2
公开(公告)日：2011-07-14
申请号：PCT/US2011/020418
申请日：2011-01-06
申请人： ERRICO, Joseph P. , MUGRAGE, Benjamin , TURCHI, Ignatius , SILLS, Matthew , HERRON, Jeffrey D. , LODATO, Nicholas J. , ONG, Jane , PINE, Corey , FEAVER, William J. , ALLOCCO, John , WINES, Pam
发明人： ERRICO, Joseph P. , MUGRAGE, Benjamin , TURCHI, Ignatius , SILLS, Matthew , HERRON, Jeffrey D. , LODATO, Nicholas J. , ONG, Jane , PINE, Corey , FEAVER, William J. , ALLOCCO, John , WINES, Pam
IPC分类号： A61K31/496
CPC分类号： C07D215/26 , A61K31/47 , A61K31/4709 , A61K31/496 , A61K45/06 , C07C335/26 , C07D207/48 , C07D209/08 , C07D239/42 , C07D239/47 , C07D239/52 , C07D285/135 , C07D295/26 , C07D307/54 , C07D401/12 , C07D401/14 , C07D403/12 , C07D405/06 , C07D405/14 , C07D409/06 , C07D409/14 , C07D417/14 , G06F19/16
摘要： Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.
摘要翻译： 本文提供了具有抗增殖作用的化合物。 还提供了可以调节包含二聚化臂和结构域间连接臂（例如EGFR）的多结构域蛋白的活性的化合物，其中未束缚的延长构象是活性状态并且束缚构象是非活性状态，导致自我抑制构型 。 还提供了用于鉴定这些化合物的方法和药效团。 其他方面提供增殖性疾病，病症或病症的方法或治疗性治疗，例如与EGFR相关的疾病，病症或病症。
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公开(公告)号：WO2011085126A2
公开(公告)日：2011-07-14
申请号：PCT/US2011/020414
申请日：2011-01-06
申请人： ERRICO, Joseph P. , MUGRAGE, Benjamin , TURCHI, Ignatius , SILLS, Matthew , ONG, Jane , ALLOCCO, John , WINES, Pam
发明人： ERRICO, Joseph P. , MUGRAGE, Benjamin , TURCHI, Ignatius , SILLS, Matthew , ONG, Jane , ALLOCCO, John , WINES, Pam
IPC分类号： C07D401/02
CPC分类号： C07D215/26 , A61K31/47 , A61K31/4709 , A61K31/496 , A61K45/06 , C07C335/26 , C07D207/48 , C07D209/08 , C07D239/42 , C07D239/47 , C07D239/52 , C07D285/135 , C07D295/26 , C07D307/54 , C07D401/12 , C07D401/14 , C07D403/12 , C07D405/06 , C07D405/14 , C07D409/06 , C07D409/14 , C07D417/14 , G06F19/16
摘要： Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.
摘要翻译： 本文提供具有抗增殖作用的化合物。 还提供了可以调节包含二聚化臂和跨域系链例如EGFR的多结构域蛋白质的活性的化合物，其中无阻塞的扩展构象是活性状态，并且系留构象是无活性状态，导致自身抑制构型 。 还提供了用于鉴定这些化合物的方法和药效团。 其他方面为增殖性疾病，病症或病症（例如与EGFR相关的病症）提供方法或治疗方法。
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