Citation: Zhaoyong Kang, Shen Li, Yan Li, Jingfeng Song, Yangrui Peng, Yihua Chen. Small molecular inhibitors and degraders targeting STAT3 for cancer therapy: An updated review (from 2022 to 2024)[J]. Chinese Chemical Letters, ;2025, 36(7): 110447. doi: 10.1016/j.cclet.2024.110447 shu

Small molecular inhibitors and degraders targeting STAT3 for cancer therapy: An updated review (from 2022 to 2024)

Zhaoyong Kang ^{a, b, 1} ,
Shen Li ^{b, 1} ,
Yan Li ^c ,
Jingfeng Song ^a ,
Yangrui Peng ^b ,
Yihua Chen ^{a, b, *,}

a.
School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products and Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming 650500, China
b.
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
c.
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China

Received Date: 15 July 2024
Revised Date: 9 September 2024
Accepted Date: 11 September 2024
Available Online: 11 September 2024

Figures(9)

Signal transducer and activator of transcription 3 (STAT3) is a member of the transcription factors involved in regulating many physiological and pathological processes, such as cell proliferation, angiogenesis and immune escape. STAT3 has been identified as a potential therapeutic target for various cancers. Although numerous STAT3 inhibitors have been discovered and optimized to directly inhibit STAT3 activity, they are not yet authorized for clinical use and only a few have entered clinical trials. Furthermore, several proteolysis-targeting chimera (PROTAC) molecules with STAT3 degrading effects have been developed. The event-driven action of PROTAC overcome the drawbacks of STAT3, a traditional undruggable target, and addressed possible resistance to small-molecule inhibitors by degrading the entire STAT3 protein. In this review, we presented a brief introduction to STAT3 and its functions in various cancers, and systematically overviewed the pharmacological effects of inhibitors targeting different domains of STAT3 in the last three years, the structural characterization of the main scaffold, the design strategies, and the pharmacological activities of the substituents. Also, the binding patterns and interactions of some inhibitors with STAT3 were analyzed in detail and the recent advances in STAT3 degraders are also summarized. We anticipate that this perspective will contribute to the design and optimize more novel effective and specific STAT3 inhibitors or degraders for carcinoma treatment.
- STAT3,
- Small molecule inhibitors,
- Cancer therapy,
- STAT3 degraders,
- PROTAC
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沈阳化工大学材料科学与工程学院沈阳 110142