Indoximod  (Synonyms: 1-Methyl-D-tryptophan; NLG-8189)

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].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

218.25

Solid

C₁₂H₁₄N₂O₂

110117-83-4

N[C@H](CC1=CN(C)C2=CC=CC=C12)C(O)=O

Room temperature in continental US; may vary elsewhere.

• [1]. Hou DY, et al. Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophancorrelates with antitumor responses. Cancer Res. 2007 Jan 15;67(2):792-801.  [Content Brief]

  [2]. Metz R, et al. IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. Oncoimmunology. 2012;1(9):1460-1468.  [Content Brief]