05-03-2020 дата публикации
Номер: US20200069814A1
Автор:
CAI Xiang,
CHAO Minjun,
GAI Shun,
GAO Shuihong,
GUO Huihui,
GUO Zhixiang,
Huang Yuanyuan,
JIA Junxiang,
Li Wenjun,
Lin Chen,
PENG JIE,
SU Qingyu,
Tong Qianqian,
Wang Chunyan,
Xie Hongsheng,
Xu Jun,
Xu Yifang,
YANG Chengyu,
YANG Qingliang,
YANG Yanlei,
YE Hangbo,
YE Zhicang,
ZHAO Linyao,
ZHAO Robert Yongxin,
ZHOU Xiaomai,
Zhu Haifeng,
ZUO Xiaotao
A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease. 9. The conjugate compound according to claim 1 , wherein the cell-binding molecule is connected to Zand Zvia a pair of thiols formed from inter chain disulfide atoms of the cell-binding molecule.10. The conjugate compound according to claim 1 , wherein the cytotoxic molecule is selected from:(1). a chemotherapeutic agent selected from the group consisting of:a). an alkylating agent: selected from the group consisting of nitrogen mustards: chlorambucil, chlornaphazine, cyclophosphamide, dacarbazine, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, mannomustine, mitobronitol, melphalan, mitolactol, pipobroman, novembichin, phenesterine, prednimustine, thiotepa, trofosfamide, uracil mustard; CC-1065 and adozelesin, carzelesin, bizelesin or their synthetic analogues; duocarmycin and its synthetic analogues, KW-2189, CBI-TMI, or CBI dimers; benzodiazepine dimers or pyrrolobenzodiazepine (PBD) dimers, tomaymycin dimers, indolinobenzodiazepine dimers, imidazobenzothiadiazepine dimers, or oxazolidinobenzodiazepine dimers; Nitrosoureas: comprising carmustine, lomustine, chlorozotocin, fotemustine, nimustine, ranimustine; Alkylsulphonates: comprising busulfan, treosulfan, improsulfan and piposulfan); Triazenes or dacarbazine; Platinum containing compounds: comprising carboplatin, cisplatin, and oxaliplatin; aziridines, benzodopa, carboquone, meturedopa, or uredopa; ethylenimines and methylamelamines including altretamine, triethylenemel-amine, trietylenephosphoramide, triethylenethiophosphoramide and trimethylolomelamine];b). a plant alkaloid: selected from the group ...
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