Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and PROTAC-based degraders for cancer therapy

Eur J Med Chem. 2022 Jan 5:227:113967. doi: 10.1016/j.ejmech.2021.113967. Epub 2021 Nov 2.

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1), a known immunosuppressive enzyme that catalyzes the rate-limiting step in the oxidation of tryptophan (Trp) to kynurenine (Kyn), has received increasing attention as an attractive immunotherapeutic target for cancer therapy. Up to now, eleven small-molecule IDO1 inhibitors have entered clinical trials for the treatment of cancers. In addition, proteolysis targeting chimera (PROTAC) based degraders also provide prospects for cancer therapy. Herein we present a comprehensive overview of the medicinal chemistry strategies and potential therapeutic applications of IDO1 inhibitors in nonclinical trials and IDO1-PROTAC degraders.

Keywords: Cancer therapy; IDO1 degrader; IDO1 inhibitor; Indoleamine 2,3-dioxygenase 1.

Publication types

  • Review

MeSH terms

  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Molecular Structure
  • Neoplasms
  • Proteolysis / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Small Molecule Libraries