A novel CXCR4 antagonist for hematopoietic stem cell mobilization

Expert Opin Investig Drugs. 2008 Nov;17(11):1749-60. doi: 10.1517/13543784.17.11.1749.

Abstract

Background: Hematopoietic stem cell (HSC) transplantation is a treatment option for hematological malignancies. Current mobilization regimes frequently result in inadequate numbers of HSC for transplant therefore alternative methods of mobilization are required.

Objective: The chemokine receptor CXCR4 and ligand SDF-1 are integrally involved in HSC homing and mobilization. Disruption of the SDF-1/CXCR4 axis by the CXCR4 anatagonist, plerixafor, is shown to improve HSC mobilization.

Methods: The molecular and in vivo pharmacology of plerixafor and subsequent clinical development is reviewed.

Results/conclusion: Preclinical studies demonstrate that plerixafor is a selective antagonist of CXCR4 and can rapidly mobilize HSC. Clinical trials demonstrated improved HSC mobilization when plerixafor was included in the mobilization regimen. These data suggest the potential for a significant role for plerixafor in hematological disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzylamines
  • Cyclams
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / metabolism

Substances

  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • plerixafor