- Novel IDO1 inhibitors at the forefront of cancer immunotherapy: from compound screening to preclinical validation in pancreatic ductal adenocarcinoma and glioblastoma multiforme



Funding body
PRIN 2017
145.732 €

Departments and Centres



Department of Pharmaceutical Sciences


Working group

Tracey Pirali
Silvio Aprile
Silvia Fallarini
Marta Serafini

Project duration

Start date
End date

The project is part of a larger research area in the field of oncology, particularly in cancer immunotherapy. The project focuses on the discovery and preclinical development of ID01 inhibitors, an enzyme involved in immune escape, i.e. the ability of the tumour to evade the immune system.

The study derives from a virtual screening initiative carried out by Prof. Massarotti (DSF, UPO) which allowed Dr. Fallarini (DSF, UPO) to identify some hit compounds with a strong inhibitory capacity. From these, a wide library of structurally heterogeneous compounds was drawn up (Prof. Pirali: DFS, UPO), allowing the identification of a lead compound that:

  1. Revealed features of IDO1 as compared with other dioxygenes (Dr. Pallotta: Università di Perugia)
  2. Revealed greater ability than clinical candidate epacadostat in some functional samples (Dr. Ugel, Università di Verona)
  3. Revealed lower metabolic stability (Dr. Aprile: DSF, UPO)

Therefore, other inhibitors are currently under development, with the dual aim of identifying a candidate with a strong ADME profile and the ability to interfere not only with the catalytic activity of the enzyme but also with its powerful and recently-described activity of moonlighting. This will allow a contribution to research in the field of IDO1 inhibitors and to develop inhibitors with an innovative profile as compared with other compounds that have already been identified but unfortunately failed during the development process.