Identification of novel allosteric nonpeptidergic inhibitors of the human cytomegalovirus-encoded chemokine receptor US28

Bioorg Med Chem. 2010 Jan 15;18(2):675-88. doi: 10.1016/j.bmc.2009.11.060. Epub 2009 Dec 6.

Abstract

Human cytomegalovirus (HCMV) is a widespread human pathogen, possessing onco-modulatory properties. Constitutive signaling of the HCMV-encoded chemokine receptor US28 and its ability to bind a broad spectrum of chemokines might facilitate HCMV-associated tumor progression. Novel nonpeptidergic chemotypes were identified as neutral antagonists or inverse agonists on US28, that allosterically inhibit chemokine binding to US28.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology*
  • Humans
  • Imipramine / analogs & derivatives
  • Imipramine / chemistry
  • Imipramine / pharmacology*
  • Indenes / chemical synthesis
  • Indenes / chemistry
  • Indenes / pharmacology*
  • Ligands
  • Molecular Structure
  • Receptors, Chemokine / agonists
  • Receptors, Chemokine / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Viral Proteins / agonists
  • Viral Proteins / antagonists & inhibitors*

Substances

  • 2-(2,4-dichlorobenzyl)-2,3-dihydro-1H-inden-1-amine
  • Amines
  • Indenes
  • Ligands
  • Receptors, Chemokine
  • US28 receptor, Cytomegalovirus
  • Viral Proteins
  • Imipramine