1-Methyltryptophan Explained

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

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

The -isomer (-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] -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]

Notes and References

  1. Cady . SG . Sono . M . 1-Methyl--tryptophan, beta-(3-benzofuranyl)--alanine (the oxygen analog of tryptophan), and beta-3-benzo[''b'']thienyl--alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase . Archives of Biochemistry and Biophysics . 291 . 2 . 326–33 . 1991 . 1952947 . 10.1016/0003-9861(91)90142-6 .
  2. 17671174. 2007. Metz. R. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound -1-methyl-tryptophan. Cancer Research. 67. 15. 7082–7. Duhadaway. J. B.. Kamasani. U. Laury-Kleintop. L. Muller. A. J.. Prendergast. G. C.. 10.1158/0008-5472.CAN-07-1872. free.
  3. 23264892. 3525601. 2012. Metz. R. IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by -1-methyl-tryptophan. OncoImmunology. 1. 9. 1460–1468. Rust. S. Duhadaway. J. B.. Mautino. M. R.. Munn. D. H.. Vahanian. N. N.. Link. C. J.. Prendergast. G. C.. 10.4161/onci.21716.
  4. http://www.onclive.com/publications/oncology-live/2017/vol-18-no-16/ido-inhibitors-emerging-as-new-players-on-checkpoint-blockade-scene?p=2 IDO Inhibitors Emerging as New Players on Checkpoint Blockade Scene. Aug 2017
  5. Web site: NewLink Genetics. finpedia.co. 2019-05-09.
  6. Web site: NewLink Genetics Annual Report (Form 10-K). fintel.io. April 9, 2018.

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