Strategic Incorporation of Polarity in Heme-Displacing Inhibitors of Indoleamine-2,3-dioxygenase-1 (IDO1).

ABSTRACT: Indoleamine-2,3-dioxygenase-1 (IDO1) has emerged as a target of significant interest to the field of cancer immunotherapy, as the upregulation of IDO1 in certain cancers has been linked to host immune evasion and poor prognosis for patients. In particular, IDO1 inhibition is of interest as a combination therapy with immune checkpoint inhibition. Through an Automated Ligand Identification System (ALIS) screen, a diamide class of compounds was identified as a promising lead for the inhibition of IDO1. While hit 1 possessed attractive cell-based potency, it suffered from a significant right-shift in a whole blood assay, poor solubility, and poor pharmacokinetic properties. Through a physicochemical property-based approach, including a focus on lowering AlogP₉₈ via the strate

SUBMITTER: White C 

PROVIDER: S-EPMC7153270 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature