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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Di Pucchio
Tiziana
T
Istituto Superiore di Sanità, Department of Cell Biology and Neurosciences, Rome, Italy.
Danese
Silvio
S
De Cristofaro
Raimondo
R
Rutella
Sergio
S
D000818:Animals; D015551:Autoimmunity; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D007737:Kynurenine / Q000378:metabolism; D010330:Patents as Topic; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000378:metabolism
D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan