Comparison study of different indoleamine-2,3 dioxygenase inhibitors from the perspective of pharmacodynamic effects.

ABSTRACT:

Introduction

Indoleamine 2,3-dioxygenase (IDO) was a potential tumor immunotherapy target. IDO inhibitors showed inconsistent results in clinical trials, but no preclinical comparative study was reported. The purpose of this study was to evaluate the differences of representative IDO inhibitors (PCC0208009, INCB024360, NLG919) from the pharmacological perspective.

Methods

In vitro experiments included: inhibition effects on IDO activity in cell and enzyme-based assay, effects on IDO expression in HeLa cells, and enhancement of proliferation and activation of peripheral blood mononuclear cell (PBMC). In vivo experiments included: pharmacokinetics and tumor distribution in CT26-bearing mice, effects on Kyn/Trp and anti-tumor effect and immunological mechanism in CT26 and B16F1

SUBMITTER: Jiang X 

PROVIDER: S-EPMC7517983 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature