美国密歇根大学Shaomeng Wang研究团队的一项工作鉴定出一种有效的、选择性的STAT3（信号转导和转录激活因子3）小分子降解剂，其可在体内实现肿瘤的完全消退。相关论文2019年11月11日发表在《癌细胞》上。

研究人员报道了一个STAT3的小分子降解剂SD-36。SD-36在体外和体内均能有效诱导STAT3蛋白降解，并显示出比其他STAT成员更高的选择性。STAT3的诱导降解导致其在白血病和淋巴瘤细胞中的转录网络受到强烈抑制。SD-36通过诱导细胞周期停滞和/或凋亡来抑制部分急性髓细胞白血病和间变性大细胞淋巴瘤细胞系的生长。SD-36在耐受良好的剂量方案下，能够在多种异种移植小鼠模型中实现完整且持久的肿瘤消退。因此，STAT3蛋白的降解是一种有前途的癌症治疗策略。

据介绍，STAT3是潜在的癌症治疗靶标。

附：英文原文

Title: A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo

Author: 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

Issue&Volume: 2019/11/11

Abstract: Signal transducer and activator of transcription 3 (STAT3) is an attractive cancertherapeutic target. Here we report the discovery of SD-36, a small-molecule degraderof 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 ofSTAT3 results in a strong suppression of its transcription network in leukemia andlymphoma cells. SD-36 inhibits the growth of a subset of acute myeloid leukemia andanaplastic 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 mousemodels at well-tolerated dose schedules. Degradation of STAT3 protein, therefore,is a promising cancer therapeutic strategy.

DOI: 10.1016/j.ccell.2019.10.002

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30476-3