Structure-based design of new anticancer N3-Substituted quinazolin-4-ones as type I ATP-competitive inhibitors targeting the deep hydrophobic pocket of EGFR.

• Tác giả: Reem K Arafa, Ragaa Y El-Mahdy, Noha Galal, Rahma Lotfy
• Ngôn ngữ: eng
• Ký hiệu phân loại: 548.8 Physical and structural crystallography
• Thông tin xuất bản: United States : Computers in biology and medicine , 2025
• Bộ sưu tập: NCBI
• ID: 190031
• Chủ đề: 1. Structure; 2. Based; 3. Design

Tóm tắt

Epidermal growth factor receptor (EGFR) is amongst the earliest targeted kinases by small-molecule inhibitors for the management of EGFR-positive cancer types. While a few inhibitors are granted FDA approval for clinical use, discovery of new inhibitors is still of merit to enhance ligand-binding stability and subsequent enzyme inhibition. Thus, a structure-based design approach was adopted to devise a new series of twenty-nine N3-substituted quinazolin-4-ones as type I ATP-competitive inhibitors targeting the deep hydrophobic pocket of EGFR. The most active compounds demonstrated potent IC