Profiling Allosteric Modulators of CB <sub>1</sub> R with an Allosteric Fluoroprobe

Allosteric modulation of cannabinoid receptor type 1 (CB<sub>1</sub>R) offers a promising alternative to conventional therapeutic approaches using orthosteric ligands (OLs). Currently, CB<sub>1</sub>R 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 CB<sub>1</sub>R AMs without coincubation with an OL. Our allosteric tracer enables differentiation of allosteric and orthosteric ligands as well as their pharmacological profiling at CB<sub>1</sub>R. 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 CB<sub>1</sub>R with comparable affinity (pK<sub>i</sub>=5.34 and 5.67, respectively).

Authors

Institutions

Publication Details

Journal
Angewandte Chemie International Edition
Published
2025-02-18
DOI
https://doi.org/10.1002/anie.202421885
Citations
2
Primary Topic
Cannabis and Cannabinoid Research
Type
article
Field-Weighted Citation Impact
2.79

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Profiling Allosteric Modulators of CB 1 R with an Allosteric Fluoroprobe

Dmitry B. Veprintsev, Rosa Maria Vitale, Wolfgang Guba, Rudolf L. Z. Ganzoni et al.
2 citations
Angewandte Chemie International Edition
Cannabis and Cannabinoid Research
2.79
article

Profiling Allosteric Modulators of CB 1 R with an Allosteric Fluoroprobe

Dmitry B. Veprintsev, Rosa Maria Vitale, Wolfgang Guba, Rudolf L. Z. Ganzoni, Erick M. Carreira, Miroslav Kosar, Uwe Grether, Alessia Ligresti, Roman C. Sarott, Arne C. Rufer, Themiya Perera
article en
2 citations

Abstract

Allosteric modulation of cannabinoid receptor type 1 (CB<sub>1</sub>R) offers a promising alternative to conventional therapeutic approaches using orthosteric ligands (OLs). Currently, CB<sub>1</sub>R 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 CB<sub>1</sub>R AMs without coincubation with an OL. Our allosteric tracer enables differentiation of allosteric and orthosteric ligands as well as their pharmacological profiling at CB<sub>1</sub>R. 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 CB<sub>1</sub>R with comparable affinity (pK<sub>i</sub>=5.34 and 5.67, respectively).

Angewandte Chemie International EditionVol. 64(20)
Roche (Switzerland) (CH), University of Nottingham (GB), University of the Basque Country (ES), ETH Zurich (CH), Institute of Applied Science and Intelligent Systems (IT), National Research Council (IT)
Medical Research Council
Openalex Percentile: Top 12%
Cannabis and Cannabinoid Research
2.79
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.