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1.发明申请PEPTIDE MIMETIC LIGANDS OF POLO-LIKE KINASE 1 POLO BOX DOMAIN AND METHODS OF USE 审中-公开POLO-like激素的肽类化合物1 POLO BOX域及其使用方法公开(公告)号：US20140142044A1
公开(公告)日：2014-05-22
申请号：US14111540
申请日：2012-04-12
申请人： Terrence R. Burke, JR. , Wenjian Qian , Fa Liu , Kyung S. Lee , Jung-Eun Park
发明人： Terrence R. Burke, JR. , Wenjian Qian , Fa Liu , Kyung S. Lee , Jung-Eun Park
IPC分类号： C07K7/06
CPC分类号： C07K7/06 , A61K38/00 , A61K47/60 , C07K1/006 , C07K5/0827 , C12N9/12 , C12Y207/11021
摘要： Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds. The compounds of the invention have potential therapeutic activity in view of their binding and inhibitory activities towards Plk1. They are based on the amino acid sequence PLHSpT (phosphorylated Thr). The PEG moiety, when present, is covalently attached at the N-terminus. The invention also encompasses derivatives having substituents on the Pro and/or the His side chains, substituents on the phosphate group, the replacement of His with Gln, the replacement of Pro with a N-substituted Gly, the replacement of Ser with Ala, as well as HS-pT fragments with N-terminal alkoxycarbonyl group and PLHS fragments with a C-terminal glyco-imino-alkylxyalkylamide group.
摘要翻译： 提供了通过polo-box结构域结合polo样激酶的新型化合物。 在某些实施方案中，新化合物是PEG化肽。 根据本发明的聚乙二醇化肽表现出高PBD结合亲和力。 在某些实施方案中，聚乙二醇化肽还在整个细胞系统中获得活性。 本发明还提供通过马球结构域结合polo样激酶并具有减少的阴离子电荷的化合物。 还提供了聚乙二醇化肽的设计和/或合成方法及其使用方法。 本发明提供了化合物的使用方法和化合物的合成方法。 考虑到它们对Plk1的结合和抑制活性，本发明的化合物具有潜在的治疗活性。 它们基于氨基酸序列PLHSpT（磷酸化的Thr）。 存在时，PEG部分在N末端共价连接。 本发明还包括在Pro和/或His侧链上具有取代基的衍生物，磷酸基团上的取代基，用Gln取代His，用N-取代的Gly取代Pro，用Ala取代Ser，作为 以及具有N-末端烷氧基羰基的HS-pT片段和具有C-末端糖 - 亚氨基 - 烷基烷基酰胺基团的PLHS片段。
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公开(公告)号：US10266565B2
公开(公告)日：2019-04-23
申请号：US14111540
申请日：2012-04-12
申请人： Terrence R. Burke, Jr. , Fa Liu , Kyung S. Lee , Jung-Eun Park
发明人： Terrence R. Burke, Jr. , Fa Liu , Kyung S. Lee , Jung-Eun Park
摘要： Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds.
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3.发明授权Peptide mimetic ligands of polo-like kinase 1 polo box domain and methods of use 有权polo样激酶1 polo box结构域的肽模拟配体和使用方法公开(公告)号：US09175038B2
公开(公告)日：2015-11-03
申请号：US13320726
申请日：2010-05-17
申请人： Terrence R. Burke, Jr. , Fa Liu , Kyung S. Lee , Jung-Eun Park
发明人： Terrence R. Burke, Jr. , Fa Liu , Kyung S. Lee , Jung-Eun Park
摘要： Found in various eukaryotic organisms, polo-like kinases (collectively, Plks) are a conserved subfamily of Ser/Thr protein kinases that play critical roles in cell proliferation. Provided herein are compounds that specifically inhibit the activity of Plks, specifically Plk1. Further provided herein are methods for use of the compounds for the treatment of hyperproliferative disorders, particularly cancer. Also provided are uses of the compounds for the preparation of a medicament.
摘要翻译： 在各种真核生物中发现，polo样激酶（统称为Plks）是Ser / Thr蛋白激酶的保守亚家族，在细胞增殖中起关键作用。 本文提供特异性抑制Plks活性的化合物，特别是Plk1。 本文还提供了用于治疗过度增殖性疾病，特别是癌症的化合物的方法。 还提供了化合物用于制备药物的用途。
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4.发明申请PEPTIDE MIMETIC LIGANDS OF POLO-LIKE KINASE 1 POLO BOX DOMAIN AND METHODS OF USE 有权POLO-like激素的肽类化合物1 POLO BOX域及其使用方法公开(公告)号：US20120065146A1
公开(公告)日：2012-03-15
申请号：US13320726
申请日：2010-05-17
申请人： Terrence R. Burke, JR. , Fa Liu , Kyung S. Lee , Jung-Eun Park
发明人： Terrence R. Burke, JR. , Fa Liu , Kyung S. Lee , Jung-Eun Park
摘要： Found in various eukaryotic organisms, polo-like kinases (collectively, Plks) are a conserved subfamily of Ser/Thr protein kinases that play critical roles in cell proliferation. Provided herein are compounds that specifically inhibit the activity of Plks, specifically Plk1. Further provided herein are methods for use of the compounds for the treatment of hyperproliferative disorders, particularly cancer. Also provided are uses of the compounds for the preparation of a medicament.
摘要翻译： 在各种真核生物中发现，polo样激酶（统称为Plks）是Ser / Thr蛋白激酶的保守亚家族，在细胞增殖中起关键作用。 本文提供特异性抑制Plks活性的化合物，特别是Plk1。 本文还提供了用于治疗过度增殖性疾病，特别是癌症的化合物的方法。 还提供了化合物用于制备药物的用途。
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公开(公告)号：US20080139456A1
公开(公告)日：2008-06-12
申请号：US11575723
申请日：2005-09-30
申请人： Terrence R. Burke , Zhen-Dan Shi , Shinya Oishi , Fa Liu
发明人： Terrence R. Burke , Zhen-Dan Shi , Shinya Oishi , Fa Liu
CPC分类号： C07K5/06113 , A61K38/00 , C07K5/06191 , C07K5/0812 , C07K5/0827
摘要： Disclosed are compounds for inhibiting the binding of an SH2 domain-containing protein, for example, a compound of formula (I): FORMULA (I) wherein R1 is a lipophile; R2, in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; R3 is, for example, hydrogen, azido, amino, oxalylamino, carboxy alkyl, alkoxycarbonyl alkyl, aminocarbonyl alkyl, or alkyl carbonylamino; R6 is a linker; AA is an amino acid; and n is 1 to 6; or a pharmaceutically acceptable salt, stereoisomer, solvate, or hydrate thereof. Also disclosed are pharmaceutical compositions and methods of use of such compounds.
摘要翻译： 公开了用于抑制含SH2结构域的蛋白质，例如式（I）的化合物：式（I）的化合物：其中R1是亲油性物质; R2与苯环组合是苯基磷酸酯模拟基团或被保护的苯基磷酸酯模拟基团; R3是例如氢，叠氮基，氨基，草酰氨基，羧基烷基，烷氧基羰基烷基，氨基羰基烷基或烷基羰基氨基; R6是连接体; AA是氨基酸; n为1〜6; 或其药学上可接受的盐，立体异构体，溶剂合物或水合物。 还公开了药物组合物和这些化合物的使用方法。
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