Indoximod

Indoximod (1-Methyl-D-tryptophan) is an orally active indoleamine 2,3-dioxygenase (IDO) pathway inhibitor. Indoximod acts as a Trp mimetic in regulating mTOR. Indoximod is an immunometabolic adjuvant used for the research of cancer^[1][2]. IC50 & Target: Ki: 19 μM (IDO)^[2] In Vitro: The IDO inhibitor 1-methyl-tryptophan exists in two stereoisomers with potentially different biological properties. The L isomer is the more potent inhibitor of IDO activity using the purified enzyme and in HeLa cell–based assays. However, the D isomer is significantly more effective in reversing the suppression of T cells created by IDO-expressing dendritic cells. The L isomer of 1-methyl-tryptophan functioned as a competitive inhibitor (K_i=19 μM), whereas the d isomer is much less effective. The DL mixture is intermediate, with a K_i of 35 μM^[1]. In Vivo: The D isomer is more efficacious as an anticancer agent in chemo-immunotherapy regimens using NSC-26271, NSC 125973, or LY 188011, when tested in mouse models of transplantable melanoma and transplantable and autochthonous breast cancer. The D isomer of 1-methyl-tryptophan specifically targets the IDO gene because the antitumor effect of d-1-methyl-tryptophan is completely lost in mice with a disruption of the IDO gene (IDO-knockout mice). Oral administration of dl-1-methyl-tryptophan in combination with NSC 125973 can elicit regression of autochthonous breast tumors^[1].