ChemicalBook Product Catalog Biochemical Engineering Amino Acids and Derivatives Tryptophan derivatives 1-Methyl-D-tryptophan

1-Methyl-D-tryptophan

Product Name1-Methyl-D-tryptophan
CAS110117-83-4
MFC12H14N2O2
MW218.25
EINECS
MOL File110117-83-4.mol

Chemical Properties

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).
pka	2.26±0.10(Predicted)
form	White to light brown crystalline powder.
color	White
optical activity	[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.
Major Application	peptide synthesis
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

Safety Information

WGK Germany	3
Storage Class	11 - Combustible Solids

MSDS

Provider	Language
SigmaAldrich	English

Usage And Synthesis

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-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.

Uses

1-Methyl-D-tryptophan is used in biological studies to determine the effect of IDO2 enzyme (indoleamine-(2,3)-dioxygenase) activity and IDO2-mediated arrest of human T cell proliferation. It reverses IDO-mediated immune suppression

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

73-22-3

74-88-4

21339-55-9

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] DE-YAN HOU. Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses.[J]. Cancer research, 2007, 67 2: 792-801. DOI:10.1158/0008-5472.can-06-2925
[2] HATEM SOLIMAN Scott A Melanie Mediavilla Varela. Indoleamine 2,3-dioxygenase: is it an immune suppressor[J]. Cancer journal, 2010, 16 4: 354-359. DOI:10.1097/ppo.0b013e3181eb3343
[3] MARIA FRIBERG. Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection[J]. International Journal of Cancer, 2002, 101 2: 151-155. DOI:10.1002/ijc.10645
[4] RICHARD METZ. IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan.[J]. Oncoimmunology, 2012, 1 9: 1460-1468. DOI:10.4161/onci.21716

1-Methyl-D-tryptophan

Chemical Properties

Safety Information

MSDS

Usage And Synthesis

Preparation Products And Raw materials

1-Methyl-D-tryptophan Supplier

1-Methyl-D-tryptophan manufacturers

Related Product Information