Structure and Plasticity of Indoleamine 2,3-Dioxygenase 1 (IDO1)

J Med Chem. 2021 Dec 23;64(24):17690-17705. doi: 10.1021/acs.jmedchem.1c01665. Epub 2021 Dec 15.


Since the discovery of the implication of indoleamine 2,3-dioxygenase 1 (IDO1) in tumoral immune resistance in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies, supported by the publication of the first crystal structure of IDO1 in 2006. More recently, it has become clear that IDO1 is an important player in various biological pathways and diseases ranging from neurodegenerative diseases to infection and autoimmunity. Its inhibition may lead to clinical benefit in different therapeutic settings. At present, over 50 experimental structures of IDO1 in complex with different ligands are available in the Protein Data Bank. Our analysis of this wealth of structural data sheds new light on several open issues regarding IDO1's structure and function.

MeSH terms

  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / chemistry*
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase