Discovery of IDO1 Inhibitors: From Bench to Bedside
Authors: George C. Prendergast, William P. Malachowski, James B. DuHadaway and Alexander J. Muller
Source: Cancer Research, Volume 77, Issue 24, pp. 6795-6811
Abstract: Small-molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) are emerging at the vanguard of experimental agents in oncology. Here, pioneers of this new drug class provide a benchto- bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds, indoximod, epacadostat, and navoximod, that were first to be evaluated as IDO inhibitors in clinical trials. As immunometabolic adjuvants to widen therapeutic windows, IDO inhibitors may leverage not only immuno-oncology modalities but also chemotherapy and radiotherapy as standards of care in the oncology clinic.