| Description: |
Indoximod (D-1MT, NLG8189) is an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor with a Ki of 19 μM. |
| In Vivo: |
The D isomer is more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamide, paclitaxel, or gemcitabine, 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 paclitaxel can elicit regression of autochthonous breast tumors[1]. |
| 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 (Ki=19 μM), whereas the d isomer is much less effective. The DL mixture is intermediate, with a Ki of 35 μM[1]. |
