Cited by 771NF-κB Signaling PathwaysNatural Compounds in Disease TreatmentSignaling Pathways in Disease

Inhibiting NF-κB activation by small molecules as a therapeutic strategy

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Gupta, Subash C., Sundaram, Chitra, Reuter, Simone, Aggarwal, Bharat B.·2010·Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Abstract

Because nuclear factor-κB (NF-κB) is a ubiquitously expressed proinflammatory transcription factor that regulates the expression of over 500 genes involved in cellular transformation, survival, proliferation, invasion, angiogenesis, metastasis, and inflammation, the NF-κB signaling pathway has become a potential target for pharmacological intervention. A wide variety of agents can activate NF-κB through canonical and noncanonical pathways. Canonical pathway involves various steps including the phosphorylation, ubiquitination, and degradation of the inhibitor of NF-κB (IκBα), which leads to the nuclear translocation of the p50-p65 subunits of NF-κB followed by p65 phosphorylation, acetylation and methylation, DNA binding, and gene transcription. Thus, agents that can inhibit protein kinases, protein phosphatases, proteasomes, ubiquitination, acetylation, methylation, and DNA binding steps have been identified as NF-κB inhibitors. Because of the critical role of NF-κB in cancer and various chronic diseases, numerous inhibitors of NF-κB have been identified. In this review, however, we describe only small molecules that suppress NF-κB activation, and the mechanism by which they block this pathway.

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Crossref · 10.1016/j.bbagrm.2010.05.004

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Authors
Gupta, S. C., Sundaram, C., Reuter, S., & Aggarwal, B. B.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Aggarwal, Bharat B.
Venue
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Publisher
Elsevier BV
Published
2010-10
Volume
1799
Issue
10-12
Pages
775-787
ISSN
1874-9399 (ISSN-L)
OpenAlex
W1973354681
Cited by
762
References
232
Citations by year
2026: 38 · 2025: 32 · 2024: 39 · 2023: 36 · 2022: 42 · 2021: 59 · 2020: 63 · 2019: 66 · 2018: 70 · 2017: 63 · 2016: 45 · 2015: 45 · 2014: 41 · 2013: 50 · 2012: 35
FWCI
3.26
Type
journal article
Language
en
Open access
Locations
  • Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (CA-16672, P01CA091844, P01CA124787, CA-124787-01A2, P30CA016672)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
NF-κB signaling, NF-κB inhibitors, small molecules, canonical NF-κB pathway, non-canonical NF-κB signaling, protein kinases, proteasome inhibitors, protein phosphatase, inflammation, cancer, chronic disease
MeSH terms
Animals, Cell Survival, Cell Transformation, Neoplastic, Gene Expression Regulation, Humans, Inflammation, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Phosphorylation, Signal Transduction, NF-kappa B, Neovascularization, Physiologic, Cell Proliferation, I-kappa B Kinase

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