4.6 Review

Discovery of STAT3 Inhibitors: Recent Advances and Future Perspectives

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Repurposing of drugs as STAT3 inhibitors for cancer therapy

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Summary: Drug repurposing is a valuable approach for rapidly introducing new cancer therapies into clinical practice. STAT3 inhibitors play a significant role in cancer treatment, but challenges remain in understanding the mechanisms of STAT3 activation and developing strategies to suppress its activity with various pharmaceutical agents.

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Summary: The study optimized proline-based STAT3 inhibitors into a new series of azetidine-2-carboxamide analogues with sub-micromolar potencies, demonstrating potential therapeutic effects on breast cancer cells.

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A 2-Benzylmalonate Derivative as STAT3 Inhibitor Suppresses Tumor Growth in Hepatocellular Carcinoma by Upregulating β-TrCP E3 Ubiquitin Ligase

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Summary: The novel small molecule CIB-6 inhibits STAT3 activation, potentiates the anti-cancer effects of IFN-α, and suppresses the migration and invasion of HCC cells by inhibiting the epithelial-mesenchymal transition process.

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Design and synthesis of 2-Substituted-4-benzyl-5-methylimidazoles as new potential Anti-breast cancer agents to inhibit oncogenic STAT3 functions

Botros Y. Beshay et al.

Summary: This study identified a novel class of compounds that alter STAT3 signaling, showing inhibitory effects on breast cancer cells, suppressing their growth and production of relevant proteins. These compounds have the potential to be new anti-cancer drug candidates targeting oncogenic STAT3 function.

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Design, synthesis and in vivo anticancer activity of novel parthenolide and micheliolide derivatives as NF-KB and STAT3 inhibitors

Binglin Zeng et al.

Summary: The study synthesized derivatives of parthenolide and micheliolide, with 9-oxomicheliolide (43) showing promising in vivo anticancer activity, particularly against glioblastoma. Compound 43 exhibited inhibition against NF-KB and STAT3 signaling pathways, induced cell apoptosis, and may function as an immunomodulator in regulating anticancer immune responses, suggesting its potential as a candidate for anticancer drug development.

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Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide

Xuebao Wang et al.

Summary: A series of N-substituted Sulfamoylbenzamide STAT3 inhibitors based on Niclosamide were designed and synthesized, with compound B12 identified as a potent inhibitor of IL-6/STAT3 signaling in cancer cell lines. In vivo studies showed that B12 was more effective than Niclosamide in suppressing tumor growth, making it a promising orally bioavailable anticancer agent for further development.

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Discovery of STAT3 and Histone Deacetylase (HDAC) Dual-Pathway Inhibitors for the Treatment of Solid Cancer

Yuhao Ren et al.

Summary: The study found that inhibiting histone deacetylases (HDACs) in breast cancer can activate the cancer-related STAT3, limiting the anti-proliferation effect of HDAC inhibitors in solid tumors. The synthesized dual-target inhibition activity derivatives exhibited potent ability to inhibit both STAT3 and HDAC.

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

Jinyun Dong et al.

Summary: STAT3 is a transcription factor regulating various biological processes, frequently abnormally activated in cancer and associated with poor prognosis and tumor progression. Targeting the STAT3 protein may be an effective strategy for treating tumors.

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John Jumper et al.

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Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

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2-Thiopyrimidine/chalcone hybrids: design, synthesis, ADMET prediction, and anticancer evaluation as STAT3/STAT5a inhibitors

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Unexpected implications of STAT3 acetylation revealed by genetic encoding of acetyl-lysine

Yael Belo et al.

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Design, Synthesis, And Evaluation Of Cyanopyridines As Anti-Colorectal Cancer Agents Via Inhibiting STAT3 Pathway

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Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein

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Discovery of new benzensulfonamide derivatives as tripedal STAT3 inhibitors

Jianpeng Guo et al.

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Linker Variation and Structure-Activity Relationship Analyses of Carboxylic Acid-based Small Molecule STAT3 Inhibitors

Francisco Lopez-Tapia et al.

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Antagonizing STAT3 activation with benzo[b]thiophene 1, 1-dioxide based small molecules

Wenda Zhang et al.

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3′-Hydroxypterostilbene Suppresses Colitis-Associated Tumorigenesis by Inhibition of IL-6/STAT3 Signaling in Mice

Ching-Shu Lai et al.

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Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

Joleen M. Hubbard et al.

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Identification of a new STAT3 dimerization inhibitor through a pharmacophore-based virtual screening approach

Giulio Poli et al.

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Discovery of oral-available resveratrol-caffeic acid based hybrids inhibiting acetylated and phosphorylated STAT3 protein

Shanshan Li et al.

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Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors

Philias Daka et al.

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Evolutions in fragment-based drug design: the deconstruction-reconstruction approach

Haijun Chen et al.

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Novel aminotetrazole derivatives as selective STAT3 non-peptide inhibitors

Jean-Rene Pallandre et al.

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Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening

Ka-Ho Leung et al.

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Suppression of cancer relapse and metastasis by inhibiting cancer stemness

Youzhi Li et al.

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Novel 2-Carbonylbenzo[b]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway

Peng Ji et al.

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Mechanisms of Jak/STAT Signaling in Immunity and Disease

Alejandro V. Villarino et al.

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Antagonizing STAT3 Dimerization with a Rhodium(III) Complex

Dik-Lung Ma et al.

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Novel Carbazole Inhibits Phospho-STAT3 through Induction of Protein-Tyrosine Phosphatase PTPN6

Shujie Hou et al.

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Fragment-based drug design and identification of HJC0123, a novel orally bioavailable STAT3 inhibitor for cancer therapy

Haijun Chen et al.

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An Update on Antitumor Activity of Naturally Occurring Chalcones

En-Hui Zhang et al.

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Analysis of Safety from a Human Clinical Trial with Pterostilbene

Daniel M. Riche et al.

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Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

Xiaolei Zhang et al.

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Design, synthesis and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein

Vijay M. Shahani et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2011)

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Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain

Brent D. G. Page et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2011)

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Sorafenib derivatives induce apoptosis through inhibition of STAT3 independent of Raf

Kuen-Feng Chen et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2011)

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Inhibiting signal transducer and activator of transcription 3: rationality and rationale design of inhibitors

Arun K. Mankan et al.

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Article Chemistry, Medicinal

Identification of Purine-Scaffold Small-Molecule Inhibitors of Stat3 Activation by QSAR Studies

Vijay M. Shahini et al.

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Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors

Jianyong Chen et al.

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Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3 Signaling Pathway

Xiaomei Ren et al.

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STATs in cancer inflammation and immunity: a leading role for STAT3

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Chalcone inhibits the activation of NF-κB and STAT3 in endothelial cells via endogenous electrophile

Yen-Chin Liu et al.

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Stattic: A small-molecule inhibitor of STAT3 activation and dimerization

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