Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and PROTAC-based degraders for cancer therapy.

Indoleamine 2,3-dioxygenase 1 (IDO1), a known immunosuppressive enzyme that catalyzes the rate-limiting step in the oxidation of tryptophan (Trp) to kynurenine (Kyn), has received increasing attention as an attractive immunotherapeutic target for cancer therapy. Up to now, eleven small-molecule IDO1 inhibitors have entered clinical trials for the treatment of cancers. In addition, proteolysis targeting chimera (PROTAC) based degraders also provide prospects for cancer therapy. Herein we present a comprehensive overview of the medicinal chemistry strategies and potential therapeutic applications of IDO1 inhibitors in nonclinical trials and IDO1-PROTAC degraders. [Display omitted] • Small molecule IDO1 inhibitors in nonclinical trials are discussed. • The PROTAC-based IDO1 degraders are also highlighted. • The rational design and SARs of novel IDO1 inhibitors are presented in detailed. [ABSTRACT FROM AUTHOR]