A theranostic probe of indoleamine 2,3-dioxygenase 1 (IDO1) for small molecule cancer immunotherapy

Eur J Med Chem. 2021 Mar 5:213:113163. doi: 10.1016/j.ejmech.2021.113163.

Ying Wu ¹, Yanhui Zhang ², Xi Chen ², Yulu Hu ², Guoqiang Dong ¹, Yuan Guo ³, Chunquan Sheng ⁴

Affiliations

1 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
2 Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, 1 Xuefu Avenue, Xi'an, 710127, China.
3 Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, 1 Xuefu Avenue, Xi'an, 710127, China. Electronic address: guoyuan@nwu.edu.cn.
4 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China. Electronic address: shengcq@hotmail.com.

PMID: 33482599 DOI: 10.1016/j.ejmech.2021.113163

Abstract

Discovering novel small molecules for Cancer Immunotherapy represents a promising but challenging strategy in future Cancer treatment. Herein, we designed the first theranostic fluorescent probes to efficiently detect and inhibit the enzymatic activity of 2,3-dioxygenase 1 (IDO1). Probe 6b is a highly active IDO1 Inhibitor (IC₅₀ = 12 nM, Cellular IC₅₀ = 10 nM), which can sensitively and specifically detect endogenous IDO1 in living cells. Furthermore, as a theranostic probe, 6b showed excellent in vivo antitumor efficacy in the CT26 xenograft mouse model as well. Therefore, it can be applied as a valuable chemical tool for better understanding the immunotherapy mechanism of IDO1 and improving the therapeutic efficiency.

Keywords

Cancer immunotherapy; IDO1; Theranostic probe.

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