Figure 2.

Indoximod mechanisms of action. Tryptophan catabolism proceeds through pathways leading to serotonin or NAD production, the latter through the kynurenine pathway which handles ~95% of Trp catabolism in mammals. Indoximod is a Trp mimetic which mTORC1 interprets as L-Trp under conditions of high Trp catabolism and autophagy. Thus, the drug acts to block the suppressive signal on mTORC1 function generated by IDO/TDO activity. Other suggested mechanisms of action include an indirect suppression of IDO2 activity; a modulation of kynurenine-regulated AHR function, which may also influence feedback on IDO1 expression and activity; and an influence on gut microbial physiology influencing systemic immunity (see the text).