1-Methyltryptophan

1-Methyltryptophan
Names
	IUPAC name 2-Amino-3-(1-methyl-1H-indol-3-yl)propanoic acid
	Other names 1-Methyl-DL-tryptophan; DL-1-Methyltryptophan; ARBRIN
Identifiers
CAS Number	26988-72-7 (D/L) ; 21339-55-9 (L) ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL504816 ; ChEMBL514172 ;
ChemSpider	88584 ;
ECHA InfoCard	100.043.765
IUPHAR/BPS	4694;
PubChem CID	98112;
	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) Key: ZADWXFSZEAPBJS-UHFFFAOYSA-N ; 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) Key: ZADWXFSZEAPBJS-UHFFFAOYSA-N;
	SMILES O=C(O)C(N)Cc2c1ccccc1n(c2)C;
Properties
Chemical formula	C12H14N2O2
Molar mass	218.26 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	verify (what is ?)
	Infobox references

1-Methyltryptophan is a chemical compound that is an inhibitor of the tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO or INDO EC 1.13.11.52).^[1] It is a chiral compound that can exist as both D- and L-isomers (enantiomers).

The L-isomer (L-1MT) inhibits IDO weakly but also serves as an enzyme substrate.

The D-isomer (D-1MT) does not inhibit IDO at all, but it can inhibit the IDO-related enzyme IDO2^[2] and restore mTOR signaling in cells starved of tryptophan due to IDO activity.^[3] D-1MT is also known as indoximod and is currently in clinical trials for cancer treatment, eg. for advanced melanoma.^[4]

References

↑ Cady, SG; Sono, M (1991). "1-Methyl-DL-tryptophan, beta-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and beta-3-benzo(b)thienyl-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase". Archives of Biochemistry and Biophysics. 291 (2): 326–33. doi:10.1016/0003-9861(91)90142-6. PMID 1952947.
↑ Metz, R; Duhadaway, J. B.; Kamasani, U; Laury-Kleintop, L; Muller, A. J.; Prendergast, G. C. (2007). "Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan". Cancer Research. 67 (15): 7082–7. doi:10.1158/0008-5472.CAN-07-1872. PMID 17671174.
↑ Metz, R; Rust, S; Duhadaway, J. B.; Mautino, M. R.; Munn, D. H.; Vahanian, N. N.; Link, C. J.; Prendergast, G. C. (2012). "IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan". OncoImmunology. 1 (9): 1460–1468. doi:10.4161/onci.21716. PMC 3525601. PMID 23264892.
↑ IDO Inhibitors Emerging as New Players on Checkpoint Blockade Scene. Aug 2017

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[1] Cady, SG; Sono, M (1991). "1-Methyl-DL-tryptophan, beta-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and beta-3-benzo(b)thienyl-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase". Archives of Biochemistry and Biophysics. 291 (2): 326–33. doi:10.1016/0003-9861(91)90142-6. PMID 1952947.

[2] Metz, R; Duhadaway, J. B.; Kamasani, U; Laury-Kleintop, L; Muller, A. J.; Prendergast, G. C. (2007). "Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan". Cancer Research. 67 (15): 7082–7. doi:10.1158/0008-5472.CAN-07-1872. PMID 17671174.

[3] Metz, R; Rust, S; Duhadaway, J. B.; Mautino, M. R.; Munn, D. H.; Vahanian, N. N.; Link, C. J.; Prendergast, G. C. (2012). "IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan". OncoImmunology. 1 (9): 1460–1468. doi:10.4161/onci.21716. PMC 3525601. PMID 23264892.

[OL-AACR-2017-4] IDO Inhibitors Emerging as New Players on Checkpoint Blockade Scene. Aug 2017