Discovery of β-amino acid substituted naphthalene sulfonamide derivatives as potent Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) protein-protein interaction inhibitors for ulcerative colitis management.

• Tác giả: Yuxin Ge, Zhengyu Jiang, Hongjin Lu, Mengchen Lu, Junjie Wang, Tingting Wu, Shicheng Xu, Qidong You, Ziquan Zhao
• Ngôn ngữ: eng
• Thông tin xuất bản: France : European journal of medicinal chemistry , 2025
• Bộ sưu tập: NCBI
• ID: 199495

Tóm tắt

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular defense system against oxidative insults. Directly inhibiting the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has emerged as a promising approach to activate Nrf2 for the treatment of diseases associated with oxidative stress. Herein, we identified β-amino acids as privileged structural fragments for designing novel naphthalene sulfonamide-based Keap1-Nrf2 PPI inhibitors. Comprehensive structure-activity relationship (SAR) exploration identified compound 19 as the optimal inhibitor with an IC