Inhibitors of indoleamine 2,3-dioxygenase: a review of novel patented lead compounds

Abstract

Importance of the field: The enzyme indoleamine 2,3-dioxygenase (IDO) regulates immune responses through the capacity to degrade the essential amino-acid tryptophan into kynurenine and other downstream metabolites that suppress effector T-cell function and favour the differentiation of regulatory T cells. The current experimental evidence indicates that IDO can be expressed by a variety of cell types, including dendritic cells, tumour cells and stromal cells. Recently, IDO has been implicated in B-cell stimulation and autoantibody production in experimental models of autoimmune diseases.

Areas covered in this review: Advances in the biochemistry of IDO and our understanding of the biological relevance of IDO-mediated tryptophan consumption to the establishment of immune tolerance are summarised and discussed. A selection of recent patents in the field are also reviewed and analysed.

What the reader will gain: Readers will gain an overview of the patented compounds with IDO inhibitory activity from an immunologist's perspective. They will also learn about the companies that are main players in the field.

Take home message: Current evidence points to IDO as a molecular target for therapeutic intervention in order to restrain unwanted inflammatory/autoimmune responses and/or to boost antitumour immunity.

Keywords::

• autoimmunity
• cancer
• dendritic cell
• haematopoietic growth factors
• immune tolerance
• indoleamine 2
• 3-dioxygenase
• regulatory T cell
• tolerance

Notes

This box summarises key points contained in the article.