The Advances of the Structure and Function of Indoleamine 2, 3- dioxygenase 1 and Its Inhibitors

Curr Protein Pept Sci. 2020;21(10):1027-1039. doi: 10.2174/1389203721666200526122304.

Abstract

Indoleamine 2, 3-dioxygenase 1 (IDO1) is the only rate-limiting enzyme outside the liver that catalyzes the oxidation and cracking of indole rings in the tryptophan along the kynurenine pathway (KP). The overactivation of IDO1 is closely related to the pathogenesis of various human immune and neurological diseases. As an important target for the treatment of many human serious diseases, including malignant tumors, the development of IDO1 inhibitors is of great practical significance. In this work, the structure and function of IDO1 both are summarized from the aspects of the signal pathway, catalytic mechanism, structural biology, and so on. Moreover, the current development status of IDO1 inhibitors is also systematically reviewed, which provides assistance for anti-cancer drug design based on the structure of receptors.

Keywords: 3-dioxygenase 1; Tumor; catalytic mechanism; drug design; indoleamine 2; signal path; structural biology.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / immunology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Depression / drug therapy
  • Depression / enzymology
  • Depression / genetics
  • Depression / immunology
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression
  • Histocompatibility, Maternal-Fetal / genetics
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / metabolism
  • Imidazoles / therapeutic use
  • Immune Tolerance
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / chemistry
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Indoles / chemical synthesis*
  • Indoles / metabolism
  • Indoles / therapeutic use
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / therapeutic use
  • Signal Transduction
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / metabolism
  • Triazoles / therapeutic use
  • Tumor Escape / drug effects

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • IDO1 protein, human
  • Imidazoles
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Indoles
  • Neuroprotective Agents
  • Triazoles