Indoximod

Names

[ Name ]:
Indoximod

[Synonym ]:
(2R)-2-amino-3-(1-methyl-1H-indol-3-yl)propanoic acid
D-Tryptophan, 1-methyl-
MFCD00274271
(2R)-2-amino-3-(1-methylindol-3-yl)propanoic acid
(R)-2-Amino-3-(1-methyl-1H-indol-3-yl)propanoic acid
Indoximod
D-1MT
1-Methyl-D-tryptophan
NLG-8189

Biological Activity

[Description]:

Indoximod (D-1MT, NLG8189) is an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor with a Ki of 19 μM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Indoleamine 2,3-Dioxygenase (IDO)

Research Areas >> Cancer

[Target]

IDO:19 μM (Ki)

[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].

[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].

[Kinase Assay]

1MT enantiomers are solubilized in DMSO containing 0.1N HCl and added at concentrations of 100, 50, and 0 µM to wells containing the reaction mixture with tryptophan (0-200 µM) followed by addition of IDO enzyme. Plates are sealed and incubated 1 hr in a humidified 37°C incubator, after which the reactions are terminated by addition of 12.5 µl 30% TCA per well. Plates are then resealed in plastic wrap, incubated 30 min at 50°C to hydrolyze the reaction product N-formylkynurenine to kynurenine, and centrifuged. Supernatants are transferred to a flat-bottom 96-well plate, mixed with 100 µl Ehrlich reagent and incubated 10 min at room temperature. Absorbance at 490 nm is read[1].

[Animal admin]

Mice: B16F10 melanoma are established in B6 mice. For administration in drinking water, D-1MT is prepared at 2 mg/mL in water supplemented with a small amount of aspartame (2 envelopes per liter) to improve acceptance by the mice, and filter sterilized. The solution is delivered in standard autoclaved drinking-water bottles. Mice drink 4.5-5.0 mL/day (similar to consumption of water without drug)[1].

[References]

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
429.3±35.0 °C at 760 mmHg

[ Melting Point ]:
242-245 â„ƒ(lit.)

[ Molecular Formula ]:
C₁₂H₁₄N₂O₂

[ Molecular Weight ]:
218.252

[ Flash Point ]:
213.4±25.9 °C

[ Exact Mass ]:
218.105530

[ PSA ]:
68.25000

[ LogP ]:
1.43

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.625

MSDS

Click to get detail MSDS

Safety Information

[ Hazard Codes ]:
Xn

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2933990090

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Tumor indoleamine 2,3-dioxygenase (IDO) inhibits CD19-CAR T cells and is downregulated by lymphodepleting drugs.

Blood 125 , 3905-16, (2015)

Although T cells expressing CD19-specific chimeric antigen receptors (CARs) are a promising new therapy for B-cell malignancies, objective responses are observed at lower frequencies in patients with ...

Rational design of indoleamine 2,3-dioxygenase inhibitors.

J. Med. Chem. 53 , 1172-89, (2010)

Indoleamine 2,3-dioxygenase (IDO) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. We have used the evolutionary docking algorit...

Amino acid metabolism inhibits antibody-driven kidney injury by inducing autophagy.

J. Immunol. 194 , 5713-24, (2015)

Inflammatory kidney disease is a major clinical problem that can result in end-stage renal failure. In this article, we show that Ab-mediated inflammatory kidney injury and renal disease in a mouse ne...