Small-molecule activator of SMUG1 enhances repair of pyrimidine lesions in DNA.

• Tác giả: Shanthi Adimoolam, Ishani Das, James M Ford, Yixuan Gao, Yong Woong Jun, Eric T Kool, Lisa McPherson, Christine S C Ng, Elizabeth R Park, Samyuktha Suresh, David L Wilson
• Ngôn ngữ: eng
• Ký hiệu phân loại: 572.86459 Biochemical genetics
• Thông tin xuất bản: Netherlands : DNA repair , 2025
• Bộ sưu tập: NCBI
• ID: 498180

Tóm tắt

A potentially promising approach to targeted cancer prevention in genetically at-risk populations is the pharmacological upregulation of DNA repair pathways. SMUG1 is a base excision repair enzyme that ameliorates adverse genotoxic and mutagenic effects of hydrolytic and oxidative damage to pyrimidines. Here we describe the discovery and initial cellular activity of a small-molecule activator of SMUG1. Screening of a kinase inhibitor library and iterative rounds of structure-activity relationship studies produced compound 40 (SU0547), which activates SMUG1 by as much as 350 ± 60 % in vitro at 100 nM, with an AC