1-Methyltryptophan

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-enantiomers.

1-Methyltryptophan
Names
Preferred IUPAC name
2-Amino-3-(1-methyl-1H-indol-3-yl)propanoic acid
Other names
1-Methyl-DL-tryptophan; DL-1-Methyltryptophan; ARBRIN; Indoximod
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.043.765
  • 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) checkY
    Key: ZADWXFSZEAPBJS-UHFFFAOYSA-N checkY
  • 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
  • O=C(O)C(N)Cc2c1ccccc1n(c2)C
Properties
C12H14N2O2
Molar mass 218.256 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references

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, such as for advanced melanoma.[4]

A U.S. patent covering salt and prodrug formulations of indoximod was issued to NewLink Genetics on August 15, 2017 providing exclusivity until at least 2036.[5][6]

References
  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.
  4. IDO Inhibitors Emerging as New Players on Checkpoint Blockade Scene. Aug 2017
  5. "NewLink Genetics". finpedia.co. Retrieved 2019-05-09.
  6. "NewLink Genetics Annual Report (Form 10-K)". fintel.io. April 9, 2018.


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