IDO

IDO inhibitors block indoleamine 2,3-dioxygenase (IDO), the heme enzyme that starts tryptophan breakdown. By depleting tryptophan and producing kynurenine metabolites, IDO dampens local T cell responses. In 1998, blocking tryptophan catabolism in pregnant mice caused T cell-mediated rejection of allogeneic fetuses. Work published in 2003 showed that tumor cells expressing IDO resist immune rejection in mice. Epacadostat, BMS-986205 and LY-3381916 are IDO1 inhibitors used in tumor immunology studies. Indoximod, a tryptophan analog, acts on the same pathway, whereas GNF-PF-3777 targets the related enzyme IDO2. IDO/TDO-IN-1 also inhibits tryptophan 2,3-dioxygenase (TDO), the liver enzyme that catalyzes the same reaction.