中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors

文献类型：期刊论文

作者Chen, Shulun1,3; Guo, Wei2,3; Liu, Xiaohua1,3; Sun, Pu2; Wang, Yi2; Ding, Chunyong1,3; Meng, Linghua2,3; Zhang, Ao1,3,4
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2019-10-01
卷号179页码:38-55
关键词Indoleamine 2,3-dioxygenase Immunotherapy Oxadiazole PD-1 Life span
ISSN号0223-5234
DOI10.1016/j.ejmech.2019.06.037
通讯作者Meng, Linghua() ; Zhang, Ao(aozhang@simm.ac.cn)
英文摘要Indoleamine 2, 3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism which is an important mechanism in immune tolerance. The small molecule epacadostat is the most advanced IDO1 inhibitor, but its phase III trials as a single agent or in combinations with PD-1 antibody failed to show appreciable objective responses. To gain more insight on the antitumor efficacy of IDO1 inhibitors, we have designed a series of analogues of epacadostat by incorporating a cyclic aminosulfonamide moiety as the sidechain capping functionality. Compound 5a was found to display significant potency against recombinant hIDO1 and hIDO1 expressed HEK293 cancer cells. This compound has improved physico-chemical properties, acceptable PK parameters as well as optimal cardiac safety. Similar to epacadostat, 5a is ineffective as single agent in the CT-26 syngeneic xenograft model, however, the combination of 5a with PD-1 antibody showed both elevated tumor growth inhibition and prolonged median life span. (C) 2019 Elsevier Masson SAS. All rights reserved.
WOS关键词IMIDAZOLEISOINDOLE DERIVATIVES ; POTENT INHIBITORS ; STAGE-III ; 2,3-DIOXYGENASE ; DISCOVERY ; CHALLENGES ; CANCER ; CELL ; IMMUNOTHERAPY ; PEMBROLIZUMAB
资助项目Chinese NSF[81430080] ; Chinese NSF[81773565] ; Chinese NSF[81703327] ; Key Program of the Frontier Science of the Chinese Academy of Sciences[160621] ; Shanghai Commission of Science and Technology[16XD1404600] ; Shanghai Commission of Science and Technology[14431900400]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000486133100004
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/288545]  
专题中国科学院上海药物研究所
通讯作者Meng, Linghua; Zhang, Ao
作者单位1.Chinese Acad Sci, SIMM, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, SIMM, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Shulun,Guo, Wei,Liu, Xiaohua,et al. Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,179:38-55.
APA Chen, Shulun.,Guo, Wei.,Liu, Xiaohua.,Sun, Pu.,Wang, Yi.,...&Zhang, Ao.(2019).Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,179,38-55.
MLA Chen, Shulun,et al."Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 179(2019):38-55.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。