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

• Published in: Journal of hematology and oncology Vol. 14; no. 1; p. 68
• Main Authors: Tang, Kai, Wu, Ya-Hong, Song, Yihui, Yu, Bin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21-04-2021; BioMed Central; BMC
• Subjects: Acids; Breast cancer; Cancer; Cancer immunotherapy; Cancer therapy; Care and treatment; Cell cycle; Clinical trials; Cytokines; Drug therapy; Enzymes; Hematology; Heme; IDO1 inhibitors; Immune escape; Immune system; Immunotherapy; Kinases; Lymphocytes; Medical prognosis; Medical research; Medicine, Experimental; Melanoma; Metabolism; Metabolites; Oncology; Oxidation; Product development; Prognosis; PROTAC degraders; Proteins; Proteolysis; Review; Tryptophan; Tryptophan 2,3-dioxygenase; Tumor necrosis factor-TNF; Tumors; Vaccines; PROTAC degraders; IDO1 inhibitors; Immune escape; Cancer therapy
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-021-01080-8

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.