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

Caspar, B., Cocchiara, P., Melet, A., Van Emelen, K., Van der Aa, A., Milligan, G. and Herbeuval, J.-P. (2022) CXCR4 as a novel target in immunology: moving away from typical antagonists. Future Drug Discovery, 4(2), FDD77. (doi: 10.4155/fdd-2022-0007) (PMID:35875591) (PMCID:PMC9298491)

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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.

Item Type:Articles
Additional Information:P Cocchiara and G Milligan are supported by the EU (H2020-MSCA Program, Grant Agreement 860229-ONCORNET 2.0). The group of J-P Herbeuval is supported by the Agence nationale de Recherche (grant number ANR-21-CE15-0048 X4Inflam).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milligan, Professor Graeme
Authors: Caspar, B., Cocchiara, P., Melet, A., Van Emelen, K., Van der Aa, A., Milligan, G., and Herbeuval, J.-P.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Future Drug Discovery
Publisher:Newlands Press
ISSN:2631-3316
ISSN (Online):2631-3316
Published Online:19 July 2022
Copyright Holders:Copyright © 2022 Caspar, Birgit
First Published:First published in Future Drug Discovery 4(2):FDD77
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306583ONCORNET 2.0Graeme MilliganEuropean Commission (EC)860229Institute of Molecular, Cell & Systems Biology