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Papers of the Week
Discovery of the first selective, small-molecule GFRα2/3 inhibitors through DNA-encoded library technology.
Authors
Johnson SL, Missig G, Wang M, Ouk K, Gupta K, Nho Nguyen H, Fern Toh M, Szu-Yu Ho T, Gray D, Zhang H, Mi Choi-Sledeski Y, Barberis C, Stone DJ, Pin S, Lim JAbstract
Studies have shown that disrupting the formation of the ligand-RET-GFRα complex could be an effective way of treating pain and itch. Compared to traditional high-throughput screens, DNA encoded libraries (DELs) have distinguished themselves as a powerful technology for hit identification in recent years. The present work demonstrates the use of DEL technology identifying compound 16 as the first GFRa2/GFRa3 small molecule inhibitor (0.1/0.2 μM respectively) selective over RET. This molecule represents an opportunity to advance the development of small-molecule inhibitors targeting the GFRα-RET interface for the treatment of pain and itch.