Design, Synthesis and Pharmacological Characterization of the First Photoswitchable Small-Molecule Agonist for the Atypical Chemokine Receptor 3.

ABSTRACT: Photopharmacology offers the promise of optical modulation of cellular signaling in a spatially and temporally controlled fashion with light-sensitive molecules. This study presents the first small-molecule photoswitchable agonist for an atypical G protein-coupled receptor (GPCR), the atypical chemokine receptor 3 (ACKR3). Inspired by a known benzylpiperidine-based ACKR3 agonist scaffold, 12 photoswitchable azobenzene-containing analogs were synthesized and characterized for their interaction with ACKR3. After analysis of concise Structure-Photochemistry and Structure-Affinity Relationships (SAR), compound 3e was selected as the best photoswitchable ACKR3 agonist in the series. Compound 3e can be effectively switched from its thermodynamically stable trans state to the

SUBMITTER: Berenger S 

PROVIDER: S-EPMC11886650 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature