Scientists find molecules that block β-arrestins and prolong GLP-1 signaling

Robert Lefkowitz's lab at Duke University identified three drug-like compounds that directly block β-arrestins, the proteins that dampen cellular signals. In lab tests they prolonged GLP-1 pathway signaling, including during stimulation with semaglutide (Ozempic and Wegovy), without targeting the receptor itself.

• Three compounds prevent β-arrestin recruitment to GPCRs
• G protein signaling stayed intact, including at the GLP-1 receptor
• Cmpd-5 binds a previously unknown pocket on β-arrestin (allosteric inhibition)
• The work is published in Nature after more than a decade of research