Orally bioavailable isothioureas block function of the chemokine receptor CXCR4 in vitro and in vivo

J Med Chem. 2008 Dec 25;51(24):7915-20. doi: 10.1021/jm801065q.


The interaction of the chemokine receptor CXCR4 with its ligand CXCL12 is involved in many biological processes such as hematopoesis, migration of immune cells, as well as in cancer metastasis. CXCR4 also mediates the infection of T-cells with X4-tropic HIV functioning as a coreceptor for the viral envelope protein gp120. Here, we describe highly potent, selective CXCR4 inhibitors that block CXCR4/CXCL12 interactions in vitro and in vivo as well as the infection of target cells by X4-tropic HIV.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Chemistry, Pharmaceutical / methods
  • Chemokine CXCL12 / chemistry
  • Chemokines / metabolism
  • Drug Design
  • HIV Envelope Protein gp120 / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Rats
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / chemistry*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Thiourea / chemistry*


  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Chemokines
  • HIV Envelope Protein gp120
  • Receptors, CXCR4
  • Thiourea