The DOI matches its Crossref record; 170 of the 170 references it cites were found in a registry or an index.
Recent Update on Development of Small-Molecule STAT3 Inhibitors for Cancer Therapy: From Phosphorylation Inhibition to Protein Degradation
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“CCD has a large hydrophilic surface predominantly involved in the recruitment of STAT3 to its receptor [50], which is essential not only for its activation via SH2 domain‐mediated receptor binding but also for its activation via phosphorylation [51] and nuclear translocation [52].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [50]
In the citing paper
“STAT3 has six common structural motifs, namely, NTD, CCD, DBD, the linker domain, the Src homology 2 domain (SH2), and the transactivation domain [50].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [50]
Citations
Cites
1 retracted
Identification of Purine-Scaffold Small-Molecule Inhibitors of Stat3 Activation by QSAR Studies
Shahani, V. M., Yue, P., Haftchenary, S., Zhao, W. M., Lukkarila, J. L., Zhang, X., Ball, D. P., Nona, C. N., Gunning, P. T., & Turkson, J. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100224d · Cited by 40
RetractedSTATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383
Darnell, J. E. (1997) · Science · doi:10.1126/science.277.5332.1630 · Cited by 3,979
Revisiting STAT3 signalling in cancer: new and unexpected biological functions
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3818 · Cited by 2,137
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486
Indoleamine 2,3-dioxygenase and tumor-induced tolerance
Munn, D. H., & Mellor, A. L. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31178 · Cited by 1,093
Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue
Yuan, Z.-L., Guan, Y.-J., Chatterjee, D., & Chin, Y. E. (2005) · Science · doi:10.1126/science.1105166 · Cited by 790
Siddiquee, K., Zhang, S., Guida, W. C., Blaskovich, M. A., Greedy, B. M., Lawrence, H. R., Yip, M. L. R., Jove, R., McLaughlin, M. M., Lawrence, N. J., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609757104 · Cited by 741
Marzec, M., Zhang, Q., Goradia, A., Raghunath, P. N., Liu, X., Paessler, M. E., Wang, H. Y., Wysocka, M., Cheng, M. M., Ruggeri, B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810958105 · Cited by 731
A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo
Bai, L., Zhou, H., Xu, R., Zhao, Y., Chinnaswamy, K., McEachern, D., Chen, J., Yang, C.-Y., Liu, Z., Wang, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.002 · Cited by 652
Research works printed but not linked: 2
- Kusaba T., 2006, Oncol. Rep., 15, 1445
- Liu L., 2015, Int. J. Clin. Exp. Pathol., 8, 9202
Cited by
Sorted by citations
Targeting cytokine and chemokine signaling pathways for cancer therapy
Yi, M., Li, T., Niu, M., Zhang, H., Wu, Y., Wu, K., & Dai, Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01868-3 · Cited by 528
Bromodomain and extraterminal (BET) proteins: biological functions, diseases and targeted therapy
Wang, Z., Zhang, Z.-C., Wu, Y., Pi, Y., Lou, S., Liu, T., Lou, G., & Yang, C. Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01647-6 · Cited by 251
Dong, J., Li, Y., Hu, C., Cheng, X., & Qin, J. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108488 · Cited by 193
Self-citationProtein degradation technology: a strategic paradigm shift in drug discovery
Li, H., Dong, J., Cai, M., Xu, Z., Cheng, X., & Qin, J. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01146-7 · Cited by 96
Self-citationTargeting Undruggable Transcription Factors with PROTACs: Advances and Perspectives
Li, Y., Song, J. H., Zhou, P., Zhou, J., & Xie, S. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00691 · Cited by 91
Metadata
- 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
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
