Article
作者: Missig, Galen ; Nguyen, Hanh Nho ; Ho, Tammy Szu-Yu ; Johnson, Shea L ; Choi-Sledeski, Yong Mi ; Lim, Jongwon ; Toh, May Fern ; Gray, David ; Pin, Sokhom ; Gupta, Kushali ; Ouk, Kosalvisal ; Wang, Minghua ; Stone, David J ; Barberis, Claude ; Zhang, Hongjun
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.