Discovery of dual PARP/NAMPT inhibitors for the treatment of BRCA wild-type triple-negative breast cancer.

• Tác giả: Sheng Jiang, Zepeng Liao, Jie Mao, Qi Miao, Guoqing Shen, Jun Tong, Dexiang Wang, Kaizhen Wang, Kuojun Zhang, Wanheng Zhang, Zhiyi Zhang
• Ngôn ngữ: eng
• Thông tin xuất bản: England : Bioorganic & medicinal chemistry letters , 2025
• Bộ sưu tập: NCBI
• ID: 690355

Tóm tắt

Simultaneous inhibition of poly(ADP-ribose) polymerase (PARP) and nicotinamide phosphoribosyltransferase (NAMPT) has been shown to be synergistically effective against breast cancer susceptibility (BRCA) wild-type triple-negative breast cancer (TNBC) through synthetic lethality, which may be explored to broaden the clinical utility of PARP inhibitors. Herein, we report the discovery of dual PARP/NAMPT inhibitors through a pharmacophore linking approach. The lead compound 13j with potent inhibitory activity against both PARP1 and NAMPT (IC