CXCR4 as a novel target in immunology: moving away from typical antagonists.

Abstract

CXCR4 has been a target of interest in drug discovery for numerous years. However, so far, most if not all studies focused on finding antagonists of CXCR4 function. Recent studies demonstrate that targeting a minor allosteric pocket of CXCR4 induces an immunomodulating effect in immune cells expressing CXCR4, connected to the TLR pathway. Compounds binding in this minor pocket seem to be functionally selective with inverse agonistic properties in selected GPCR signaling pathways (Gi activation), but additional signaling pathways are likely to be involved in the immunomodulating effects. In depth research into these CXCR4-targeted immunomodulators could lead to novel treatment options for (auto)-immune diseases.

• Authors: Birgit Caspar, Pietro Cocchiara, Armelle Melet, Kristof Van Emelen, Annegret Van der Aa, Graeme Milligan, Jean-Philippe Herbeuval
• Journal: Future drug discovery (Future Drug Discov) Vol. 4 Issue 2 Pg. FDD77 (Jun 2022) ISSN: 2631-3316 [Electronic] England
• PMID: 35875591 (Publication Type: Journal Article, Review)
• Copyright: © 2022 Caspar, Birgit.