Cited by 236Cytokine Signaling Pathways and InteractionsProtein Degradation and InhibitorsHeterocyclic Compound Synthesis and Bioactivity

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

Dong, Jinyun, Cheng, Xiang-Dong, Zhang, Wei-Dong, Qin, Jiang-Jiang·2021·Journal of Medicinal Chemistry

DOI 10.1021/acs.jmedchem.1c00629

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Abstract

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.

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Authors: Dong, J., Cheng, X.-D., Zhang, W.-D., & Qin, J.-J.
Affiliations: Chinese Academy of Sciences (CN)
Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, China
School of Pharmacy, Naval Medical University, Shanghai 200433, China
Corresponding author: Qin, Jiang-Jiang
ORCID: Dong, Jinyun
Qin, Jiang-Jiang
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2021-06-25
Volume: 64
Issue: 13
Pages: 8884-8915
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/acs.jmedchem.1c00629
OpenAlex: W3175064583
Cited by: 232
References: 170
Citations by year: 2026: 45 · 2025: 57 · 2024: 56 · 2023: 44 · 2022: 28 · 2021: 2
FWCI: 4.06
Type: journal article
Language: en
Open access: closed
Licence: doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-045 (stm-asf)
Locations: Journal of Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81903842)
Natural Science Foundation of Zhejiang Province (LQ21B020003, LR21H280001)
Zhejiang Province (2020ZZ005)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
Keywords: STAT3, small molecule inhibitors, protein degraders, phosphorylation inhibition, cancer therapy, drug design, inhibitor optimization, structural features, clinical trials, chemoresistance, tumor progression
MeSH terms: Drug Development, Antineoplastic Agents, Humans, Neoplasms, Phosphorylation, Molecular Structure, STAT3 Transcription Factor, Small Molecule Libraries

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

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