Recent Update on Development of Small-Molecule STAT3 Inhibitors for Cancer Therapy: From Phosphorylation Inhibition to Protein Degradation,Journal of Medicinal Chemistry

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Recent Update on Development of Small-Molecule STAT3 Inhibitors for Cancer Therapy: From Phosphorylation Inhibition to Protein Degradation
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2021-06-25 , DOI: 10.1021/acs.jmedchem.1c00629
Jinyun Dong _{1,

2} , Xiang-Dong Cheng _{1,

2} , Wei-Dong Zhang ₃ , Jiang-Jiang Qin _{1,

2}

Affiliation

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates various biological processes, including proliferation, metastasis, angiogenesis, immune response, and chemoresistance. In normal cells, STAT3 is tightly regulated to maintain a transiently active state, while persistent STAT3 activation occurs frequently in cancers, associating with a poor prognosis and tumor progression. Targeting the STAT3 protein is a potentially promising therapeutic strategy for tumors. Although none of the STAT3 inhibitors has been marketed yet, a few of them have succeeded in entering clinical trials. This Review aims to systematically summarize the progress of the last 5 years in the discovery of directive STAT3 small-molecule inhibitors and degraders, focusing primarily on their structural features, design strategies, and bioactivities. We hope this Review will shed light on future drug design and inhibitor optimization to accelerate the discovery process of STAT3 inhibitors or degraders.

中文翻译：

用于癌症治疗的小分子 STAT3 抑制剂开发的最新进展：从磷酸化抑制到蛋白质降解

信号转导和转录激活因子 3 (STAT3) 是一种转录因子，可调节各种生物过程，包括增殖、转移、血管生成、免疫反应和化学抗性。在正常细胞中，STAT3 受到严格调控以维持短暂的活跃状态，而持续的 STAT3 激活在癌症中经常发生，这与不良预后和肿瘤进展相关。靶向 STAT3 蛋白是一种潜在的有前途的肿瘤治疗策略。尽管 STAT3 抑制剂尚未上市，但其中一些已成功进入临床试验。本综述旨在系统地总结过去 5 年在发现定向 STAT3 小分子抑制剂和降解剂方面的进展，主要关注它们的结构特征、设计策略、和生物活性。我们希望这篇综述能够阐明未来的药物设计和抑制剂优化，以加速 STAT3 抑制剂或降解剂的发现过程。

更新日期：2021-07-08

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