Disrupted target binding with acryloyl group as potential Bcr-Abl/C-Src dual kinase inhibitor optimization strategies with maintained antitumor activity.

• Tác giả: Grace Shiahuy Chen, Ji-Wang Chern, Hsin-Yi Chiang, Ching Lin, Chao-Wu Yu
• Ngôn ngữ: eng
• Ký hiệu phân loại: 338.6046 Organization of production
• Thông tin xuất bản: England : Bioorganic & medicinal chemistry letters , 2025
• Bộ sưu tập: NCBI
• ID: 253942

Tóm tắt

Current CML treatments often suffer from undesired side effects. Herein we report the computation-assisted optimization of Bcr-Abl/C-Src dual kinase inhibitor. We surmised the improved toxicity profile was achieved via disrupted ligand-target binding. The development of compound 21b highlighted our strategy with ∼1000-fold weaker Bcr-Abl/C-Src inhibition but same level of antiproliferation compared to that of bosutinib. We demonstrated that the introduction of acryloyl group could serves as a potential strategy to maintain antitumor activity.