Xiaoyu Zhou, Cheng Zhao, Haiyan Xu, Yixiang Xu, Li Zhan, Pei Wang, Jingyi He, Taotao Lu, Yueling Gu, Yan Yang, Chanjuan Xu, Yiyang Chen, Yuxuan Liu, Yue Zeng, Fuyun Tian, Qian Chen, Xin Xie, Jianfeng Liu, Hailan Hu, Jian Li, Yueming Zheng, Jiangtao Guo, Zhaobing Gao
Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying potassium channel 4.1 (Kir4.1) in the lateral habenula ameliorates depression-like phenotypes in mice. However, Kir4.1 remains an elusive drug target for depression. Here, we discovered a series of Kir4.1 inhibitors through high-throughput screening. Lys05, the most potent one thus far, effectively suppressed native Kir4...
February 14, 2024: Nature Chemical Biology