公开(公告)号：US20110301108A1

公开(公告)日：2011-12-08

申请号：US13125530

申请日：2009-10-24

申请人： Jian-Ting Zhang ,  Jing Qi ,  Hui Peng ,  Zizheng Dong

发明人： Jian-Ting Zhang ,  Jing Qi ,  Hui Peng ,  Zizheng Dong

IPC分类号： A61K31/704 ,  A61P35/00 ,  A61K31/5377 ,  A61K31/4166 ,  C12N5/09 ,  A61K31/53

CPC分类号： A61K31/425 ,  A61K31/54

摘要： Disclosed herein are materials and methods for sensitizing multidrug resistant cancer cells that express ABCG2 and related proteins members of a family of ATP-binding transporter superfamily that mediate drug efflux found in some types of multidrug resistant caner cells. A series of compounds, including (N-(4-chlorophenyl)-2-[(6-{[4,6-di(4-morpholinyl)-1,3,5-tri-azin-2-yl]amino}-1,3-benzothiazol-2-yl)sulfanyl]acetamide), specifically inhibits ABCG2 and can be used to boost the bio-avail-ability of one or more effective cancer killing drugs, making it possible to use certain widely used chemotherapeutic reagent to treat multidrug resistance cancers. Using these compounds in combination with chemotherapeutic drugs that are substrates for ABCG2 and related proteins may also find utility in treating cancer cells that are not currently identified as multi-drug resistant Additionally, these compounds appear to accelerate the intercellular degradation of ABCG2 and related proteins. They are not toxic to animals at levels at which they effect the activity of ABCG2 expressed in multi-drug resistant cancer lines.

摘要翻译： 本文公开了用于敏化表达ABCG2的多药耐药性癌细胞的物质和方法，以及介导某些类型的多药耐药性细胞中发现的药物流出的ATP结合转运蛋白超家族的相关蛋白质成员。 一系列化合物，包括（N-（4-氯苯基）-2 - [（6 - {[4,6-二（4-吗啉基）-1,3,5-三氮杂萘-2-基]氨基} -1,3-苯并噻唑-2-基）硫烷基]乙酰胺），特异性抑制ABCG2，可用于提高一种或多种有效的癌症杀伤药物的生物利用度，使得可以使用某些广泛使用的化学治疗试剂 治疗多药耐药性癌症。 将这些化合物与作为ABCG2和相关蛋白质的底物的化学治疗药物联合使用也可用于治疗目前尚未被鉴定为多药耐药的癌细胞。另外，这些化合物似乎加速了ABCG2和相关蛋白质的细胞间降解。 它们在影响多药耐药性癌细胞系中表达的ABCG2活性的水平下对动物无毒性。

公开(公告)号：US20150094353A1

公开(公告)日：2015-04-02

申请号：US14496384

申请日：2014-09-25

申请人： Jian-Ting Zhang

发明人： Jian-Ting Zhang

IPC分类号： C07D207/44

CPC分类号： C07D207/44 ,  A61K31/402

摘要： The present invention provides STAT3 inhibitors which preferentially suppress proliferation of cancer over non-cancer cells and inhibit migration and invasion of malignant cells. The inhibitors of the present invention selectively inhibit STAT3 binding to DNA without affecting the activation and dimerization of STAT3. Furthermore, the inhibitors of the present invention inhibit expression of STAT3 downstream target genes and STAT3 binding to chromatin in situ.

摘要翻译： 本发明提供优先抑制癌细胞增殖的STAT3抑制剂，并抑制恶性细胞的迁移和侵袭。 本发明的抑制剂选择性抑制STAT3与DNA的结合，而不影响STAT3的活化和二聚化。 此外，本发明的抑制剂抑制STAT3下游靶基因和STAT3原位结合染色质的表达。

公开(公告)号：US20180296557A1

公开(公告)日：2018-10-18

申请号：US15573867

申请日：2016-05-13

申请人： Jian-Ting Zhang ,  Jing-Yuan Liu

发明人： Jian-Ting Zhang ,  Jing-Yuan Liu

IPC分类号： A61K31/4985 ,  A61P35/02

CPC分类号： A61K31/4985 ,  A61P35/02 ,  G01N33/5011

摘要： Methods for treating various cancers by administering one or more compounds that target the dimeric protein survivin are disclosed. Pharmaceutical compositions containing such compounds are also disclosed, along with general methods of identifying anti-cancer compounds that target oncogenic dimeric proteins. Exemplary compounds that can be used in the disclosed methods of treatment and pharmaceutical compositions have the chemical structure.

公开(公告)号：US09382204B2

公开(公告)日：2016-07-05

申请号：US14496384

申请日：2014-09-25

申请人： Jian-Ting Zhang

发明人： Jian-Ting Zhang

IPC分类号： C07D207/44

CPC分类号： C07D207/44 ,  A61K31/402

摘要： The present invention provides STAT3 inhibitors which preferentially suppress proliferation of cancer over non-cancer cells and inhibit migration and invasion of malignant cells. The inhibitors of the present invention selectively inhibit STAT3 binding to DNA without affecting the activation and dimerization of STAT3. Furthermore, the inhibitors of the present invention inhibit expression of STAT3 downstream target genes and STAT3 binding to chromatin in situ.

摘要翻译： 本发明提供优先抑制癌细胞增殖的STAT3抑制剂，并抑制恶性细胞的迁移和侵袭。 本发明的抑制剂选择性抑制STAT3与DNA的结合，而不影响STAT3的活化和二聚化。 此外，本发明的抑制剂抑制STAT3下游靶基因和STAT3原位结合染色质的表达。

公开(公告)号：US08455252B2

公开(公告)日：2013-06-04

申请号：US13125530

申请日：2009-10-24

申请人： Jian-Ting Zhang ,  Jing Qi ,  Hui Peng ,  Zizheng Dong

发明人： Jian-Ting Zhang ,  Jing Qi ,  Hui Peng ,  Zizheng Dong

IPC分类号： A61K31/425 ,  A61K31/54

CPC分类号： A61K31/425 ,  A61K31/54

摘要： Disclosed herein are materials and methods for sensitizing multidrug resistant cancer cells that express ABCG2 and related proteins members of a family of ATP-binding transporter superfamily that mediate drug efflux found in some types of multidrug resistant cancer cells. A series of compounds, including (N-(4-chlorophenyl)-2-[(6-{[4,6-di(4-morpholinyl)-1,3,5-tri-azin-2-yl]amino}-1,3-benzothiazol-2-yl)sulfanyl]acetamide), specifically inhibits ABCG2 and can be used to boost the bio-avail-ability of one or more effective cancer killing drugs, making it possible to use certain widely used chemotherapeutic reagent to treat multidrug resistance cancers. Using these compounds in combination with chemotherapeutic drugs that are substrates for ABCG2 and related proteins may also find utility in treating cancer cells that are not currently identified as multi-drug resistant. Additionally, these compounds appear to accelerate the intercellular degradation of ABCG2 and related proteins. They are not toxic to animals at levels at which they effect the activity of ABCG2 expressed in multi-drug resistant cancer lines.

摘要翻译： 本文公开了用于敏化多药耐药性癌细胞的材料和方法，所述多药耐药性癌细胞表达ABCG2和ATP结合转运蛋白超家族的相关蛋白质成员，其介导某些类型的多重耐药性癌细胞中发现的药物流出。 一系列化合物，包括（N-（4-氯苯基）-2 - [（6 - {[4,6-二（4-吗啉基）-1,3,5-三氮杂萘-2-基]氨基} -1,3-苯并噻唑-2-基）硫烷基]乙酰胺），特异性抑制ABCG2，可用于提高一种或多种有效的癌症杀伤药物的生物利用度，使得可以使用某些广泛使用的化学治疗试剂 治疗多药耐药性癌症。 将这些化合物与作为ABCG2和相关蛋白质的底物的化学治疗药物组合也可用于治疗目前未被鉴定为多重耐药性的癌细胞。 此外，这些化合物似乎加速了ABCG2和相关蛋白的细胞间降解。 它们在影响多药耐药性癌细胞系中表达的ABCG2活性的水平下对动物无毒性。