Identification of a CXCR4 antagonist, a T140 analog, as an anti-rheumatoid arthritis agent

FEBS Lett. 2004 Jul 2;569(1-3):99-104. doi: 10.1016/j.febslet.2004.05.056.


Several recent papers support the involvement of an interaction between stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, chemokine receptor CXCR4, in memory T cell migration in the inflamed rheumatoid arthritis (RA) synovium. Analogs of the 14-mer peptide T140 were previously found to be specific CXCR4 antagonists that were characterized as not only HIV-entry inhibitors but also anti-cancer-metastatic agents. In this study, a T140 analog, 4F-benzoyl-TN14003, was proven to inhibit CXCL12-mediated migration of human Jurkat cells and mouse splenocyte in a dose-dependent manner in vitro (IC(50)=0.65 and 0.54 nM, respectively). Furthermore, slow release administration by subcutaneous injection (s.c.) of 4F-benzoyl-TN14003 using an Alzet osmotic pump significantly suppressed the delayed-type hypersensitivity response induced by sheep red blood cells in mice, and significantly ameliorated clinical severity in collagen-induced arthritis in mice. As such, T140 analogs might be attractive lead compounds for chemotherapy of RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology*
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / drug therapy*
  • Cell Movement / drug effects
  • Collagen
  • Humans
  • Jurkat Cells
  • Mice
  • Oligopeptides / pharmacology*
  • Oligopeptides / therapeutic use
  • Receptors, CXCR4 / antagonists & inhibitors*


  • Antirheumatic Agents
  • Oligopeptides
  • Receptors, CXCR4
  • Collagen
  • T140 peptide