The DOI matches its Crossref record; 231 of the 232 references it cites were found in a registry or an index.
Inhibiting NF-κB activation by small molecules as a therapeutic strategy
Open accessAbstract
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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“NF-kappB (NF-KB) has been studied for more than 25 years and is known to be expressed in all cell types, where it is involved in the oxidative stress mechanism by the expression of numerous genes, such as the cytokines, and plays a major role in the pathology of inflammatory disease [104,105].”
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Metadata
- 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)
- PMC
- PMC2955987
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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