4.5 Review

Novel inhibitors of the STAT3 signaling pathway: an updated patent review (2014-present)

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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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Summary: In this study, we identified a number of highly potent and selective STAT3 inhibitors, with compound 39 showing promising inhibition of phosphorylation of STAT3 and suppression of downstream signaling pathways. Moreover, compound 39 demonstrated significant effects on cell growth, migration, and invasion of TNBC cells, as well as tumor growth inhibition in both cell line-derived and patient-derived xenograft models in mice.

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Summary: Researchers provided an overview of STAT3 inhibitors and examined the latest research results in cancer patients. They discussed recent publications since 2015 and ongoing clinical trials on anti-STAT3 agents in cancer patients. Future challenges include developing non-peptide small-molecule inhibitors of STAT3 and enhancing understanding of STAT3's role in modulating immune response.

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Rational drug design of benzothiazole-based derivatives as potent signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors

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Summary: The study provides evidence supporting STAT3 as a therapeutic target in cancer, with compound B19 showing promising activity against IL-6/STAT3 signaling pathway and potent antiproliferative effects in cancer cell lines. The research efforts also revealed the binding mode of B19 in STAT3 SH2 domain, suggesting its potential as a therapeutic STAT3 inhibitor for cancer treatment.

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

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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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Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization

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Linlin Chen et al.

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Design, synthesis and activity of BBI608 derivatives targeting on stem cells

Qifan Zhou et al.

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Bt354 as a new STAT3 signaling pathway inhibitor against triple negative breast cancer

Yue Chen et al.

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Targeting the IL-6/JAK/STAT3 signalling axis in cancer

Daniel E. Johnson et al.

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AlloFinder: a strategy for allosteric modulator discovery and allosterome analyses

Min Huang et al.

NUCLEIC ACIDS RESEARCH (2018)

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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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HJC0152, a novel STAT3 inhibitor with promising anti-tumor effect in gastric cancer

Xiaoxia Jiang et al.

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Improved Method for the Identification and Validation of Allosteric Sites

Kun Song et al.

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Targeted protein degradation by PROTACs

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Lidia Avalle et al.

CYTOKINE (2017)

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

Joleen M. Hubbard et al.

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Small-Molecule PROTACS: New Approaches to Protein Degradation

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Optimization of pyrazole-containing 1,2,4-triazolo-[3,4-b]thiadiazines, a new class of STAT3 pathway inhibitors

Matthew G. LaPorte et al.

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Small-molecule kinase inhibitors: an analysis of FDA-approved drugs

Peng Wu et al.

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HCS Campaign to Identify Selective Inhibitors of IL-6-Induced STAT3 Pathway Activation in Head and Neck Cancer Cell Lines

Paul A. Johnston et al.

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A STAT inhibitor patent review: progress since 2011

Ping-Shan Lai et al.

EXPERT OPINION ON THERAPEUTIC PATENTS (2015)

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Impact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcriptional Activity

Tiancen Hu et al.

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Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity

Claudia Mertens et al.

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

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Galiellalactone Is a Direct Inhibitor of the Transcription Factor STAT3 in Prostate Cancer Cells

Nicholas Don-Doncow et al.

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Allosite: a method for predicting allosteric sites

Wenkang Huang 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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Discovery of Novel STAT3 Small Molecule Inhibitors via in Silico Site-Directed Fragment-Based Drug Design

Wenying Yu et al.

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Discovery of O-Alkylamino-Tethered Niclosamide Derivatives as Potent and Orally Bioavailable Anticancer Agents

Haijun Chen et al.

ACS MEDICINAL CHEMISTRY LETTERS (2013)

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Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation

Heehyoung Lee et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

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Antagonism of the Stat3-Stat3 Protein Dimer with Salicylic Acid Based Small Molecules

Steven Fletcher et al.

CHEMMEDCHEM (2011)

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A novel sequence in the coiled-coil domain of Stat3 essential for its nuclear translocation

J Ma et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)

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Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation

J Turkson et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2001)

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Inhibition of interleukin-6 signaling by galiellalactone

M Weidler et al.

FEBS LETTERS (2000)

Review Biochemistry & Molecular Biology

STAT proteins and transcriptional responses to extracellular signals

CM Horvath

TRENDS IN BIOCHEMICAL SCIENCES (2000)

Review Biochemistry & Molecular Biology

The biology of Stat4 and Stat6

AL Wurster et al.

ONCOGENE (2000)

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STATs in oncogenesis

T Bowman et al.

ONCOGENE (2000)