Beta-adrenoceptors (ß-AR) are prototypical G proteincoupled receptors and important pharmacological targets for many diseases. Indeed, a number of approved drugs target these receptors due to their key role on many physiological functions. Among other examples, we encounter ß1-AR antagonists (ß- Blockers), which constitute the first-line therapy for the treatment of heart diseases, and ß2-AR agonists, which act as bronchodilators for the treatment of breathing pathologies. Considering the relevance of these receptors, achieving a reversible and localised control of their activity would provide a powerful tool, both for its research applications and its clinical potential. In this context, photopharmacology arises as a potent approach. Photopharmacology is an emerging field based on the use of synthetic light-regulated molecules to allow reversible spatiotemporal control of target receptors in native tissues. These ligands have the potential to provide a precise and controllable therapeutic action with increased efficacy and reduced side effects. Moreover, the fine regulation on demand of the receptor activation state is of great interest for their study in non-modified cells, tissues and organisms. The present project provides the first proof of concept for beta-adrenoceptor photopharmacology. We first designed and synthesised libraries of lightregulated compounds in order to regulate ß-AR activity with spatiotemporal precision. Subsequent testing highlighted the successful development of compounds with promising pharmacological properties which can be reversibly and irreversibly controlled by light. The discovered molecules enable a fine control of ß-AR in their native environment that will certainly open the door to innovative research procedures and may inspire future personalized therapies targeting these receptors
