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

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. [Display omitted] •A series of novel environmentally sensitive IDO1 probes were successfully designed.•Probes 4 and 6b sensitively and specifically detected endogenous IDO1 in living cells.•Theranostic probe 6b showed potent in vivo efficacy in CT26 xenograft mouse model.