Targeting Stimulator of Interferon Genes (STING): A Medicinal Chemistry Perspective

J Med Chem. 2020 Apr 23;63(8):3785-3816. doi: 10.1021/acs.jmedchem.9b01039. Epub 2019 Dec 20.

Abstract

Stimulator of interferon genes (STING) is an adaptor protein that induces the secretion of type I interferons and proinflammatory cytokines and is triggered by cytosolic DNA of pathogen and host origins. Given that STING is a mediator in the immune system, pharmacological modulation of STING has shown viable therapeutic effects for pathogen infection, cancer, and inflammatory diseases. In the past decade, the substantial development in this field has encouraged the discovery of STING modulators. Here, we will summarize the current understanding of STING structure, survey the status quo of STING modulators, compare established bioassay methods, review the chemical structures and bioactivities of agonists and inhibitors, and propose suggestions and insights for the future exploitation of STING modulators.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / metabolism
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / metabolism
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Chemistry, Pharmaceutical / methods*
  • Drug Delivery Systems / methods*
  • Humans
  • Membrane Proteins / agonists
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Protein Structure, Secondary
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Membrane Proteins
  • STING1 protein, human