Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy

被引：256
作者：
Tang, Kai [1 ,2 ]
Wu, Ya-Hong [3 ]
Song, Yihui [1 ,2 ]
Yu, Bin [1 ,2 ,4 ]
机构：
[1] Zhengzhou Univ, Minist Educ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China
[2] Zhengzhou Univ, Minist Educ, Key Lab Adv Drug Preparat Technol, Zhengzhou 450001, Peoples R China
[3] Zhengzhou Univ, Sch Life Sci, Zhengzhou 450001, Peoples R China
[4] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Peoples R China
来源：
JOURNAL OF HEMATOLOGY & ONCOLOGY | 2021年 / 14卷 / 01期
基金：
中国博士后科学基金; 中国国家自然科学基金;
关键词：
Immune escape; IDO1; inhibitors; PROTAC degraders; Cancer therapy; TRYPTOPHAN CATABOLISM; KYNURENINE PATHWAY; CELL PROLIFERATION; CRYSTAL-STRUCTURE; T-CELLS; DISCOVERY; INDOLEAMINE-2,3-DIOXYGENASE; COMBINATION; CHALLENGES; IMMUNE;
D O I：
10.1186/s13045-021-01080-8
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme that catalyzes the oxidation of L-tryptophan. Functionally, IDO1 has played a pivotal role in cancer immune escape via catalyzing the initial step of the kynurenine pathway, and overexpression of IDO1 is also associated with poor prognosis in various cancers. Currently, several small-molecule candidates and peptide vaccines are currently being assessed in clinical trials. Furthermore, the "proteolysis targeting chimera" (PROTAC) technology has also been successfully used in the development of IDO1 degraders, providing novel therapeutics for cancers. Herein, we review the biological functions of IDO1, structural biology and also extensively summarize medicinal chemistry strategies for the development of IDO1 inhibitors in clinical trials. The emerging PROTAC-based IDO1 degraders are also highlighted. This review may provide a comprehensive and updated overview on IDO1 inhibitors and their therapeutic potentials.
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页数：21
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