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Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy
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Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy
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Journal Article
Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy
2021
Overview
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.
