1-methyl-D-Tryptophan

Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine, leading to the production of NAD+ via the kynurenine pathway. The overexpression of IDO in tumors and tumor-draining lymph nodes induces immune tolerance and enhances tumor growth in vivo.{26962,26961} 1-methyl-D-Tryptophan is an inhibitor of IDO (IC50 = 7 µM) that is effective in vivo.{26963,26959} In mice, 1-methyl-D-tryptophan prevents T-cell anergy triggered by dendritic cells overexpressing IDO.{26959} It augments the antitumor and antiviral immunoresponse of CD8+ T-cells and reduces tumor volume in mice with xenografts overexpressing IDO.{26962,26961} 1-methyl-D-Tryptophan, in combination with chemotherapy, causes regression of tumors and prolongs survival.{26962,26960} Surprisingly, 1-methyl-D-tryptophan induces the expression of IDO in human ovarian carcinoma SKOV3 cells in culture.{26960}