Sigma-2 receptor: past, present and perspectives on multiple therapeutic exploitations

Future Med Chem. 2018 Aug 1;10(16):1997-2018. doi: 10.4155/fmc-2018-0072. Epub 2018 Jul 3.

Abstract

Identification of sigma-2 receptor (sig-2R) has been controversial. Nevertheless, interest in sig-2R is high for its overexpression in tumors and potentials in oncology. Additionally, sig-2R antagonists inhibit Aβ binding at neurons, blocking the cognitive impairments of Alzheimer's disease. The most representative classes of sig-2R ligands are herein treated with focus on compounds that served to study sig-2R biology and to produce sig-2R: fluorescent ligands; multifunctional anticancer agents; and targeting nanoparticles. Although fluorescent ligands serve as 'green' pharmacological tools, sig-2R-multifunctional conjugates and sig-2R-targeted nanoparticles show how sig-2R targeting increases the activity of anticancer drugs in tumors with reduced toxicity. Altogether, this review draws a picture of the multiple approaches of sig-2R ligands in cancer therapy and as Alzheimer's disease modifying disease agents.

Keywords: multifunctional sigma-2 receptor ligands; sigma-2 receptor fluorescent ligands; sigma-2 receptor ligands; sigma-2 receptor targeted delivery; sigma-2 receptors.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Drug Discovery* / methods
  • Humans
  • Ligands
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Receptors, sigma / agonists
  • Receptors, sigma / antagonists & inhibitors*
  • Receptors, sigma / chemistry
  • Receptors, sigma / metabolism*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*

Substances

  • Ligands
  • Receptors, sigma
  • Small Molecule Libraries
  • sigma-2 receptor