Design, Synthesis and Biological Evaluation of Phenyl Urea Derivatives as IDO1 Inhibitors.

ABSTRACT: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing intracellular enzyme that catalyzes the first and rate-determining step of tryptophan metabolism and is an important immunotherapeutic target for the treatment of cancer. In this study, we designed and synthesized a new series of compounds as potential IDO1 inhibitors. These compounds were then evaluated for inhibitory activity against IDO1 and tryptophan 2,3-dioxygenase (TDO). Among them, the three phenyl urea derivatives i12, i23, i24 as showed potent IDO1 inhibition, with IC₅₀ values of 0.1-0.6 μM and no compound exhibited TDO inhibitory activity. Using molecular docking, we predicted the binding mode of compound i12 within IDO1. Compound i12 was further investigated by determining its in vivo phar

SUBMITTER: Zhou C 

PROVIDER: S-EPMC7144934 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature