Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.

Original publication




Journal article


Eur J Med Chem

Publication Date





284 - 301


Cancer immunotherapy, Enzyme inhibition, High throughput screening, In silico drug design, Indoleamine 2,3-dioxygenase, Molecular dynamics simulations, Structure–activity relationship, Tryptophan metabolism, Animals, Antifungal Agents, Dose-Response Relationship, Drug, Enzyme Inhibitors, High-Throughput Screening Assays, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice, Molecular Dynamics Simulation, Molecular Structure, Structure-Activity Relationship