Publications

@article{Kosar2025-la,

title = {Profiling allosteric modulators of CB1R with an allosteric  fluoroprobe},

author = {Miroslav Kosar and Themiya Perera and Rudolf L Z Ganzoni and Roman C Sarott and Leire Borrega-Roman and Rosa Maria Vitale and Alessia Ligresti and Arne C Rufer and Wolfgang Guba and Uwe Grether and Erick M Carreira and Dmitry B Veprintsev and David A Sykes},

doi = {10.1002/anie.202421885},

year  = {2025},

date = {2025-05-01},

urldate = {2025-05-01},

journal = {Angew. Chem. Int. Ed Engl.},

volume = {64},

number = {20},

pages = {e202421885},

publisher = {Wiley},

abstract = {Allosteric modulation of cannabinoid receptor type 1 (CB1R) 

 offers a promising alternative to conventional therapeutic 

 approaches using orthosteric ligands (OLs). Currently, CB1R 

 allosteric modulators (AMs) are characterized based on their 

 ability to modulate binding or functional response of OLs, 

 preventing isolation of individual contributions by allosteric 

 and orthosteric ligands. Herein, we develop the first allosteric 

 fluoroprobe and attendant FRET-based assay allowing for the 

 direct profiling of CB1R AMs without coincubation with an OL. 

 Our allosteric tracer enables differentiation of allosteric and 

 orthosteric ligands as well as their pharmacological profiling 

 at CB1R. The utility of this work is highlighted by addressing 

 ambiguities surrounding the binding of cannabidiol (CBD). CBD 

 was found to interact with both allosteric and orthosteric sites of CB1R with comparable affinity (pKi=5.34 and 5.67, 

 respectively).},

keywords = {Allosteric modulators, Cannabinoid Receptor Type 1 (CB1R), Fluoroprobe, G protein-coupled receptors, TR-FRET},

pubstate = {published},

tppubtype = {article}

}