Rational Design of a Potent, Selective, and Metabolically Stable CDK9 Inhibitor to Counteract Osimertinib Resistance through Mcl-1 Suppression and Enhanced BRD4 Co-Targeting.

• Tác giả: Jinlei Bian, Li Feng, Alexander V Finko, Jiali Huang, Zhiyu Li, Yifang Liu, Feihai Ma, Shiqi Wu, Tizhi Wu, Yifan Xu, Shijing Yu, Xiankang Zhang
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Journal of medicinal chemistry , 2025
• Bộ sưu tập: NCBI
• ID: 55712

Tóm tắt

Overcoming osimertinib resistance in NSCLC treatment remains a significant clinical challenge. CDK9 has emerged as a promising target due to its critical role in sustaining oncogenic transcriptional programs, particularly via Mcl-1 regulation. Herein, we report the structure-guided optimization of a previously identified CDK9 inhibitor (