CXCR4 As a Novel Target in Immunology: Moving Away from Typical Antagonists

Overview

Journal Future Drug Discov

Date 2022 Jul 25

PMID 35875591

Authors

Birgit Caspar

Pietro Cocchiara

Armelle Melet

Kristof Van Emelen

Annegret Van der Aa

Graeme Milligan

Jean-Philippe Herbeuval

Affiliations

Soon will be listed here.

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 (G 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.

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