共 42 条
Establishment of a human indoleamine 2, 3-dioxygenase 2 (hIDO2) bioassay system and discovery of tryptanthrin derivatives as potent hIDO2 inhibitors
被引:33
作者:

Li, Juanjuan
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Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China

Li, Yang
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Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China

Yang, Dan
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Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China

Hu, Nan
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Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China

Guo, Zhanling
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Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China

Kuang, Chunxiang
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机构:
Tongji Univ, Dept Chem, Siping Rd 1239, Shanghai 200092, Peoples R China Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China

Yang, Qing
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机构:
Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China
East China Univ Sci & Technol, SCICB, 130 Meilong Rd, Shanghai 200237, Peoples R China Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China
机构:
[1] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Songhu Rd 2005, Shanghai 200438, Peoples R China
[2] Tongji Univ, Dept Chem, Siping Rd 1239, Shanghai 200092, Peoples R China
[3] East China Univ Sci & Technol, SCICB, 130 Meilong Rd, Shanghai 200237, Peoples R China
基金:
高等学校博士学科点专项科研基金;
中国国家自然科学基金;
关键词:
Indoleamine;
2;
3-dioxygenase;
IDO2 bioassay system;
IDO2;
inhibitor;
Tryptanthrin derivatives;
TRYPTOPHAN DEGRADATION;
QUINOLINIC ACID;
2,3-DIOXYGENASE;
IDO2;
ENZYME;
EXPRESSION;
PURIFICATION;
METABOLISM;
DISTINCT;
TARGET;
D O I:
10.1016/j.ejmech.2016.07.013
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
As an analogue of IDO1 (indoleamine 2, 3-dioxygenase 1), the well-known new therapeutic target, IDO2 is receiving increased attention. Herein, the expression and purification of recombinant human IDO2 (hIDO2) and the establishment of a hIDO2 bioassay system on both enzymatic and cellular levels are described. Nine tryptanthrin derivatives were screened for potential hIDO2 inhibitory activities, and their Ki values, enzymatic and cellular IC50 values, as well as the types of inhibition were measured. The typtanthrin derivatives 5i, 5c and 5d (especially 5i) were found to be potent hIDO2 inhibitors with superior efficiency far better than that of the most frequently-used inhibitor L-1-MT. Two ultimate purposes of the present study have been achieved: establishing an IDO2 bioassay system and screening novel IDO2 inhibitors that can be used (directly or with some modifications) for potential therapeutic applications. (C) 2016 Elsevier Masson SAS. All rights reserved.
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页码:171 / 179
页数:9
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