Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3)

Dekkers, Sebastian; Comez, Dehan; Karsai, Noemi; Arimont-Segura, Marta; Canals, Meritxell; Caspar, Birgit; de Graaf, Chris; Kilpatrick, Laura E.; Leurs, Rob; Kellam, Barrie; Hill, Stephen J.; Briddon, Stephen J.; Stocks, Michael J.

Abstract

The atypical chemokine receptor 3 (ACKR3) is a receptor that induces cancer progression and metastasis in multiple cell types. Therefore, new chemical tools are required to study the role of ACKR3 in cancer and other diseases. In this study, fluorescent probes, based on a series of small molecule ACKR3 agonists, were synthesized. Three fluorescent probes, which showed specific binding to ACKR3 through a luminescence-based NanoBRET binding assay (pKd ranging from 6.8 to 7.8) are disclosed. Due to their high affinity at the ACKR3, we have shown their application in both competition binding experiments and confocal microscopy studies showing the cellular distribution of this receptor.

Citation

Dekkers, S., Comez, D., Karsai, N., Arimont-Segura, M., Canals, M., Caspar, B., de Graaf, C., Kilpatrick, L. E., Leurs, R., Kellam, B., Hill, S. J., Briddon, S. J., & Stocks, M. J. (2023). Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3). ACS Medicinal Chemistry Letters, 15(1), 143–148. https://doi.org/10.1021/acsmedchemlett.3c00469

• Journal Article Type: Letter
• Acceptance Date: Nov 29, 2023
• Online Publication Date: Dec 8, 2023
• Publication Date: Dec 8, 2023
• Deposit Date: Dec 11, 2023
• Publicly Available Date: Dec 11, 2023
• Journal: ACS Medicinal Chemistry Letters
• Electronic ISSN: 1948-5875
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Pages: 143–148
• DOI: https://doi.org/10.1021/acsmedchemlett.3c00469
• Keywords: Chemokine receptor; ACKR3; CXCR7; Fluorescent probes; BODIPY; NanoBRET
• Public URL: https://nottingham-repository.worktribe.com/output/28152638
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsmedchemlett.3c00469
• Additional Information: © 2023 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.