| Identification | Back Directory | [Name]
1-METHYL-D-TRYPTOPHAN | [CAS]
110117-83-4 | [Synonyms]
NLG-8189
Me-D-Trp
IndoxiMod
1-Me-D-Trp
D-Trp(Me)-OH
H-D-Trp(1-Me)-OH
Indoximod (NLG-8189）
1-METHYL-D-TRYPTOPHAN
1-Methyl-D-tryptophane
D-Tryptophan, 1-methyl-
1-METHYL-D-TRYPTOPHAN 95%
1-METHYL-D-TRYPTOPHAN USP/EP/BP
(R)-2-amino-3-(1-methyl-1H-indol-3-yl)propanoic acid
(2R)-2-amino-3-(1-methyl-1H-indol-3-yl)propanoic acid
INDOXIMOD;1-METHYL-D-TRYPTOPHAN;1-METHYL-D-TRYPTOPHANE | [Molecular Formula]
C12H14N2O2 | [MDL Number]
MFCD00274271 | [MOL File]
110117-83-4.mol | [Molecular Weight]
218.25 |
| Chemical Properties | Back Directory | [Melting point ]
242-245 °C(lit.)
| [alpha ]
12.4o (C = 2 IN ACETIC ACID) | [Boiling point ]
429.3±35.0 °C(Predicted) | [density ]
1.28 | [storage temp. ]
Keep in dark place,Sealed in dry,Room Temperature | [solubility ]
Soluble in DMSO (greater than 25 mg/ml). | [form ]
White to light brown crystalline powder. | [pka]
2.26±0.10(Predicted) | [color ]
White | [Optical Rotation]
[α]22/D +12.4°, c = 2 in acetic acid | [Water Solubility ]
Soluble to 5 mM in water with gentle warming | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. | [InChI]
InChI=1S/C12H14N2O2/c1-14-7-8(6-10(13)12(15)16)9-4-2-3-5-11(9)14/h2-5,7,10H,6,13H2,1H3,(H,15,16)/t10-/m1/s1 | [InChIKey]
ZADWXFSZEAPBJS-SNVBAGLBSA-N | [SMILES]
C(O)(=O)[C@@H](CC1C2=C(C=CC=C2)N(C)C=1)N |
| Hazard Information | Back Directory | [Description]
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.1,2 1-methyl-D-Tryptophan is an inhibitor of IDO (IC50 = 7 μM) that is effective in vivo.3,4 In mice, 1-methyl-D-tryptophan prevents T-cell anergy triggered by dendritic cells overexpressing IDO.4 It augments the antitumor and antiviral immunoresponse of CD8+ T-cells and reduces tumor volume in mice with xenografts overexpressing IDO.1,2 1-methyl-D-Tryptophan, in combination with chemotherapy, causes regression of tumors and prolongs survival.1,5 Surprisingly, 1-methyl-D-tryptophan induces the expression of IDO in human ovarian carcinoma SKOV3 cells in culture.5 | [Uses]
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. 1-methyl-D-Tryptophan is an inhibitor of IDO (IC50 = 7 μM) that is effective in vivo. In mice, 1-methyl-D-tryptophan prevents T-cell anergy triggered by dendritic cells overexpressing IDO. It augments the antitumor and antiviral immunoresponse of CD8+ T-cells and reduces tumor volume in mice with xenografts overexpressing IDO. 1-methyl-D-Tryptophan, in combination with chemotherapy, causes regression of tumors and prolongs survival. Surprisingly, 1-methyl-D-tryptophan induces the expression of IDO in human ovarian carcinoma SKOV3 cells in culture. | [reaction suitability]
reaction type: solution phase peptide synthesis | [Synthesis]
General procedure for the synthesis of acacia alkaloids from L-tryptophan and iodomethane: 10.2 g of L-tryptophan was dissolved in 130 mL of dimethylsulfoxide (DMSO), and 5 g of sodium hydroxide was added in batches over a 30-minute period under nitrogen protection. After addition, the reaction system was stirred at room temperature for 1 h. Subsequently, the reaction system was cooled to 0 °C. A 30 mL solution of DMSO with 7.46 g of iodomethane was slowly added dropwise over 30 min. After the dropwise addition was completed, the reaction was continued for 15 hours. After completion of the reaction, 50 mL of water was added to the system to quench the reaction. The reaction mixture was poured into 400 mL of ether and a large solid was precipitated and filtered. The resulting solid was dissolved in water and the pH was adjusted to 6-7 with concentrated hydrochloric acid, and the solid was again precipitated. Filtering was extracted and dried to give 8.7 g of white powdery product (80% yield, melting point 269°C). The product was analyzed by 1H-NMR, 13C-NMR, IR spectroscopy and mass spectrometry according to the method of Example 1. The results showed that the resulting solid product was 1-methyltryptophan with 100% purity. | [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]. | [IC 50]
IDO: 19 μM (Ki) | [storage]
Store at -20°C | [References]
1) Hou?et al. (2007),?Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses; Cancer Res.,?67?792
2) Soliman?et al. (2010),?Indoleamine 2,3-dioxygenase: is it an immune suppressor?; Cancer J.,?16?354
3) Friberg?et al. (2002),?Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T-cell mediated rejection; Int. J. Cancer,?101?151
4) Metz?et al. (2012),?IDO inhibits a tryptophan sufficiency signal that stimulates mTOR; Oncoimmunol.,?1?1460 |
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