车站3
STAT蛋白
髓系白血病
体内
癌症研究
白血病
斯达
淋巴瘤
小分子
生物
细胞凋亡
免疫学
生物化学
生物技术
作者
Longchuan Bai,Haibin Zhou,Renqi Xu,Yujun Zhao,Krishnapriya Chinnaswamy,Donna McEachern,Jianyong Chen,Chao‐Yie Yang,Zhaomin Liu,Mi Wang,Liu Liu,Hui Jiang,Bo Wen,Praveen Kumar,Jennifer L. Meagher,Duxin Sun,Jeanne A. Stuckey,Shaomeng Wang
出处
期刊:Cancer Cell
[Elsevier]
日期:2019-11-01
卷期号:36 (5): 498-511.e17
被引量:379
标识
DOI:10.1016/j.ccell.2019.10.002
摘要
Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Here we report the discovery of SD-36, a small-molecule degrader of STAT3. SD-36 potently induces the degradation of STAT3 protein in vitro and in vivo and demonstrates high selectivity over other STAT members. Induced degradation of STAT3 results in a strong suppression of its transcription network in leukemia and lymphoma cells. SD-36 inhibits the growth of a subset of acute myeloid leukemia and anaplastic large-cell lymphoma cell lines by inducing cell-cycle arrest and/or apoptosis. SD-36 achieves complete and long-lasting tumor regression in multiple xenograft mouse models at well-tolerated dose schedules. Degradation of STAT3 protein, therefore, is a promising cancer therapeutic strategy.
科研通智能强力驱动
Strongly Powered by AbleSci AI