1425944-33-7Relevant academic research and scientific papers
Structure-activity relationship studies on Bax activator SMBA1 for the treatment of ER-positive and triple-negative breast cancer
Liu, Gang,Yin, Tao,Kim, Hyejin,Ding, Chunyong,Yu, Zhuo,Wang, Hong,Chen, Haiying,Yan, Ruping,Wold, Eric A.,Zou, Hao,Liu, Xi,Ding, Ye,Shen, Qiang,Zhou, Jia
, p. 589 - 605 (2019/06/20)
In an effort to develop novel Bax activators for breast cancer treatment, a series of diverse analogues have been designed and synthesized based on lead compound SMBA1 through several strategies, including introducing various alkylamino side chains to have a deeper access to S184 pocket, replacing carbon atoms with nitrogen, and reducing the nitro group of 9H-fluorene scaffold. Compounds 14 (CYD-2-11) and 49 (CYD-4-61) have been identified to exhibit significantly improved antiproliferative activity compared to SMBA1, with IC50 values of 3.22 μM and 0.07 μM against triple-negative breast cancer MDA-MB-231 and 3.81 μM and 0.06 μM against ER-positive breast cancer MCF-7 cell lines, respectively. Mechanism of action studies of compound 49 indicated that it can activate Bax protein to induce cytochrome c release and regulate apoptotic biomarkers, leading to cancer cell apoptosis. Further in vivo efficacy studies of compounds 14 and 49 in nude mice bearing MDA-MB-231 tumor xenografts demonstrated that these drug candidates can significantly suppress tumor growth, indicating their therapeutic potential for the treatment of breast cancer.
