Qinhong Luo, Yue Ma, Huiting Liang, Yuan Feng, Na Liu, Chenshan Lian, Lizhi Zhu, Yuxin Ye, Zhihong Liu, Zhanfeng Hou, Sijin Chen, Yaqi Wang, Chuan Dai, Chunli Song, Min Zhang, Zhipeng He, Yun Xing, Wanjin Zhong, Shuiming Li, Jianlong Wu, Fei Lu, Feng Yin, Zigang Li
Lysine-specific demethylase 1 (LSD1) is a promising therapeutic target, especially in cancer treatment. Despite several LSD1 inhibitors being discovered for the cofactor pocket, none are FDA-approved. We aimed to develop stabilized peptides for irreversible LSD1 binding, focusing on unique cysteine residue Cys360 in LSD1 and SNAIL1. We created LSD1 C360-targeting peptides, like cyclic peptide S9-CMC1, using our Cysteine-Methionine cyclization strategy. S9-CMC1 effectively inhibited LSD1 at the protein level, as confirmed by MS analysis showing covalent bonding to Cys360...
November 3, 2023: Journal of Medicinal Chemistry