Development of novel CXCR4-based therapeutics

Expert Opin Investig Drugs. 2012 Mar;21(3):341-53. doi: 10.1517/13543784.2012.656197. Epub 2012 Jan 28.

Abstract

Introduction: During embryogenesis, CXCR4, a chemokine receptor, and its ligand, stromal cell-derived factor-1 (SDF-1/CXCL12), are critically involved in the development of the hematopoietic, nerve and endothelial tissues by regulating tissue progenitor cell migration, homing and survival. In adult life, the CXCR4 axis serves as the key factor for stem and immune cell trafficking. More importantly, CXCR4-CXCL12 axis plays a critical role in HIV, stem cell mobilization, autoimmune diseases, cancer and tissue regeneration. Targeting the CXCR4-CXCL12 axis, therefore, is an attractive therapeutic approach in various diseases.

Areas covered: In this review, we update current knowledge about CXCR4-CXCL12 biology, therapeutic approaches and therapeutic agents. The data presented was collected from http://www.ncbi.nlm.nih.gov/pubmed , http://clinicaltrials.gov/ , http://bloodjournal.hematologylibrary.org/ .

Expert opinion: Development of CXCR4 antagonists with increased affinity, extended pharmacokinetics and/or pharmacodynamics and with the capacity to differentially target CXCR4 may lead to a development of novel therapeutics for HIV, cancer, tissue regeneration and stem cell collection.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Cell Movement
  • Cell Survival
  • Chemokine CXCL12 / metabolism*
  • Drug Delivery Systems
  • Drug Design*
  • Humans
  • Immune System / cytology
  • Immune System / metabolism
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / metabolism
  • Stem Cells / metabolism

Substances

  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4