G protein-biased agonists enhance opioid-induced analgesia by selectively avoiding β-arrestin-2 (βarr2) signaling, which has been associated with reduced efficacy and adverse effects. Similarly, directing neurotensin receptor 1 (NTSR1) signaling toward β-arrestin pathways may promote analgesia via alternative mechanisms while minimizing side effects linked to G protein activation.

Chronic pain is a constant challenge to around 20% of the global population, and treatments to mitigate such pain often cause unacceptable side effects because the receptors and signaling pathways involved in pain sensing also drive necessary processes in the heart, lungs and liver. Opioid analgesics can be effective against chronic pain, but they can lead to tolerance and addiction.

Four months after Vertex Pharmaceuticals Inc.’s U.S. FDA nod for Journavx (suzetrigine) as the first drug targeting NaV1.8 for treating pain, Eli Lilly and Co. is joining the potential competition via a buyout of Siteone Therapeutics Inc., a privately held firm developing small-molecule sodium channel inhibitors, including a phase II-ready NaV1.8 inhibitor.