Inhibitors of CXC chemokine receptor type 4: putative therapeutic approaches in inflammatory diseases

Curr Opin Hematol. 2014 Jan;21(1):29-36. doi: 10.1097/MOH.0000000000000002.


Purpose of review: The CXC chemokine receptor type 4 (CXCR4), which is a G-protein coupled receptor, and its ligand CXCL12 play an important role in neutrophil homeostasis and inflammation. This review focuses on involvement of the CXCL12/CXCR4 axis in inflammation and different inflammatory diseases and depicts that blocking CXCR4 is an attractive therapeutic strategy.

Recent findings: Binding of CXCL12 to CXCR4 retains immature neutrophils in the bone marrow and also participates in leukocyte recruitment into inflamed tissue. The CXCL12/CXCR4 axis is also involved in several inflammatory processes and diseases including the WHIM (warts, hypogammaglobulinemia, infections and myelokathexis) syndrome, HIV, autoimmune disorders, ischemic injury, and pulmonary fibrosis.

Summary: Based on these findings, blocking CXCR4 seems to be a therapeutic strategy in inflammatory diseases. Several promising CXCR4 antagonists are in different stages of development and clinical trials. Currently, only plerixafor (AMD3100) has been approved for short-term application.

Publication types

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

MeSH terms

  • Chemokine CXCL12 / physiology*
  • DNA-Binding Proteins / therapeutic use
  • Humans
  • Inflammation / drug therapy*
  • Leukocytes / physiology
  • Neutrophils / physiology
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / physiology
  • Signal Transduction / physiology
  • Small Molecule Libraries / therapeutic use


  • Chemokine CXCL12
  • DNA-Binding Proteins
  • Receptors, CXCR4
  • Small Molecule Libraries