Targeting CXCR1/2: The medicinal potential as cancer immunotherapy agents, antagonists research highlights and challenges ahead

Eur J Med Chem. 2020 Jan 1:185:111853. doi: 10.1016/j.ejmech.2019.111853. Epub 2019 Nov 6.

Abstract

Immune suppression in the tumor microenvironment (TME) is an intractable issue in anti-cancer immunotherapy. The chemokine receptors CXCR1 and CXCR2 recruit immune suppressive cells such as the myeloid derived suppressor cells (MDSCs) to the TME. Therefore, CXCR1/2 antagonists have aroused pharmaceutical interest in recent years. In this review, the medicinal chemistry of CXCR1/2 antagonists and their relevance in cancer immunotherapy have been summarized. The development of the drug candidates, along with their design rationale, clinical status and current challenges have also been discussed.

Keywords: CXCR1/2 antagonists; Cancer; Classifications; Clinical development; Immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Humans
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Immunotherapy*
  • Molecular Structure
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Interleukin-8A / agonists*
  • Receptors, Interleukin-8A / immunology
  • Receptors, Interleukin-8B / agonists*
  • Receptors, Interleukin-8B / immunology
  • Structure-Activity Relationship

Substances

  • Immunologic Factors
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B