Photoswitchable TCB-2 for control of the 5-HT2A receptor and analysis of biased agonism

Photoswitchable TCB-2 is developed as a tool to control the serotonin 2A receptor (5-HT2AR) and to dissect biased agonism. The work designs and synthesizes a photoswitchable 5-HT2AR ligand based on the potent agonist TCB-2 and an arylazopyrazole photoswitch, enabling light-dependent control of receptor signaling. The study specifically targets pathway bias by providing a photoswitchable ligand that can modulate G protein versus beta-arrestin signaling, helping clarify how 5-HT2AR activation can lead to different downstream outcomes relevant to 5-HT2AR-targeted therapies.