2. Signaling Pathways
  3. NF-κB
  4. NF-κB

NF-κB

Nuclear factor-κB; Nuclear factor-kappaB

NF-κB

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NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory, and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory. There are five proteins in the mammalian NF-κB family: NF-κB1, NF-κB2, RelA, RelB, c-Rel.

NF-κB Isoform Specific Products:

NF-κB Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-119009
    TM-233
    		Inhibitor
    TM-233 is an inhibitor of the JAK/STAT and NF-κB signaling pathways, exhibiting significant antitumor activity. TM-233 reduces the expression of the anti-apoptotic protein Mcl-1 by inhibiting the phosphorylation of JAK2 and STAT3, and regulates its transcription by directly binding to the Mcl-1 gene promoter. Additionally, TM-233 prevents the translocation of NF-κB from the cytoplasm to the nucleus by inhibiting its DNA-binding activity, thereby reducing nuclear NF-κB expression. TM-233 shows potential in overcoming Bortezomib (HY-10227) resistance and can be applied in research related to multiple myeloma.
    TM-233
  • HY-N0613R
    Sauchinone (Standard)
    		Inhibitor
    Sauchinone (Standard) is the analytical standard of Sauchinone. This product is intended for research and analytical applications. Sauchinone is a diastereomeric lignan isolated from Saururus chinensis (Saururaceae). Sauchinone inhibits LPS-inducible iNOS, TNF-α and COX-2 expression through suppression of I-κBα phosphorylation and p65 nuclear translocation. Sauchinone has anti-inflammatory and antioxidant activity.
    Sauchinone (Standard)
  • HY-N6051R
    (-)-Maackiain (Standard)
    		Inhibitor
    (-​)​-Maackiain (Standard) is the analytical standard of (-​)​-Maackiain. This product is intended for research and analytical applications. (-)-Maackiain is a pterocarpan phytoalexin produced from Sophora flavescens. (-)-Maackiain is toxic to several genera of fungal pathogens of legume and non legume hosts. (-)-Maackiain enhances the activation of NLRP3 inflammasome, inhibits the activation of NF-κB pathway, exhibiting thereby immunostimulatory and anti-inflammatory activities. (-)-Maackiain is orally active.
    (-)-Maackiain (Standard)
  • HY-B0289R
    Erdosteine (Standard)
    		Inhibitor
    Erdosteine (Standard) is the analytical standard of Erdosteine. This product is intended for research and analytical applications. Erdosteine inhibits lipopolysaccharide (LPS)-induced NF-κB activation. Erdosteine has muco-modulatory, anti-bacterial, anti-inflammatory and anti-oxidant effects.
    Erdosteine (Standard)
  • HY-N0694R
    Schisantherin A (Standard)
    		Inhibitor
    Schisantherin A (Standard) is the analytical standard of Schisantherin A. This product is intended for research and analytical applications. Schisantherin A is a dibenzocyclooctadiene lignan. Schisantherin A inhibits p65-NF-κB translocation into the nucleus by IκBα degradation.
    Schisantherin A (Standard)
  • HY-N0802R
    Tenuigenin (Standard)
    		Inhibitor
    Tenuigenin (Standard) is the analytical standard of Tenuigenin. This product is intended for research and analytical applications. Tenuigenin is a major active component isolated from the root of the Chinese herb Polygala tenuifolia. Tenuigenin protects against S.aureus-induced pneumonia by inhibiting NF-κB activation. Tenuigenin has anti-inflammatory effect.
    Tenuigenin (Standard)
  • HY-135317D
    Emavusertib mesylate
    		Inhibitor
    Emavusertib mesylate (CA-4948 mesylate) is the mesylate salt form of Emavusertib (HY-135317). Emavusertib mesylate is an orally active inhibitor for IRAK4 (IC50=57 nM) and FLT3. Emavusertib mesylate inhibits NF-κB and MyD88 signaling pathways, reduces the generation of pro-inflammatory cytokines like IL-6 and IL-10, thereby exhibiting anti-inflammatory and anti-proliferative activities against cancer cells, leading to cell apoptosis. Emavusertib mesylate exhibits antitumor activity in mouse model.
    Emavusertib mesylate
  • HY-N8593R
    Undecane (Standard)
    		Inhibitor
    Undecane (Standard) is an analytical standard of Undecane (HY-N8593).Undecane is a potent cAMP agonist with anti-allergic and anti-inflammatory activities. Undecane inhibits degranulation and the secretion of histamine and TNF-α. Undecane reverses the increased levels of p38 phosphorylation, NF-κB transcriptional activity and target cytokine/chemokine genes, including thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and interleukin-8 (IL-8). Undecane can be used for the study of skin inflammatory disorders, such as atopic dermatitis.
    Undecane (Standard)
  • HY-W050154R
    Kojic acid (Standard)
    		Inhibitor
    Kojic acid (Standard) is the analytical standard of Kojic acid. This product is intended for research and analytical applications. Kojic acid is a substance produced by Aspergillus oryzae, with various biological activities including antitumor, insecticidal, antibacterial, antioxidant, and radioprotective effects. Kojic acid exhibits tyrosinase inhibition activity by capturing copper ions that bind to the active site of tyrosinase, preventing its activation. Tyrosinase is a key enzyme in the biosynthesis of melanin, so kojic acid can block melanin production. Additionally, kojic acid shows potential inhibition of NF-κB activity in human keratinocytes, which may also be related to the anti-melanogenic effect induced by kojic acid. Kojic acid is effective when administered orally and can also be absorbed transdermally. Nano-carrier systems prepared with kojic acid demonstrate effective delivery of anticancer drugs. Kojic acid holds promise for research in cancer, infectious diseases, and skin whitening among other fields.
    Kojic acid (Standard)
  • HY-N8085
    Icariside F2
    		Inhibitor
    Icariside F2 is a potent NF-κB inhibitor with an IC50 value of 16.25 μM. Icariside F2 is an aromatic glycoside isolated from the leaves of E. ulmoides Oliver. Icariside F2 has anti-inflammatory activity.
    Icariside F2
  • HY-N0589S
    Dehydrodiisoeugenol-d4
    Dehydrodiisoeugenol-d4 is the deuterium labeled Dehydrodiisoeugenol (HY-N0589). Dehydrodiisoeugenol can found in Myristica fragrans Houtt, shows anti-inflammatory and anti-bacterial actions. Dehydrodiisoeugenol inhibits LPS- stimulated NF-κB activation and cyclooxygenase (COX)-2 gene expression in murine macrophages.
    Dehydrodiisoeugenol-d<sub>4</sub>
  • HY-N10358
    3-(2-Hydroxyethyl) thio withaferin A
    3-(2-Hydroxyethyl) thio withaferin A is a Withaferin A derivative. Withaferin A, a steroidal lactone, inhibits NF-kB activation and targets vimentin, with potent antiinflammatory and anticancer activities. Withaferin A is an inhibitor of endothelial protein C receptor (EPCR) shedding.
    3-(2-Hydroxyethyl) thio withaferin A
Cat. No. Product Name / Synonyms Application Reactivity
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Download NF-κB Signaling Pathway Map.

NF-κB transcription factors are critical regulators of immunity, stress responses, apoptosis and differentiation. In mammals, there are five members of the transcription factor NF-κB family: RELA (p65), RELB and c-REL, and the precursor proteins NF-κB1 (p105) and NF-κB2 (p100), which are processed into p50 and p52, respectively. NF-κB transcription factors bind as dimers to κB sites in promoters and enhancers of a variety of genes and induce or repress transcription. NF-κB activation occurs via two major signaling pathways: the canonical and the non-canonical NF-κB signaling pathways[1]. 

 

The canonical NF-κB pathway is triggered by signals from a large variety of immune receptors, such as TNFR, TLR, and IL-1R, which activate TAK1. TAK1 then activates IκB kinase (IKK) complex, composed of catalytic (IKKα and IKKβ) and regulatory (NEMO) subunits, via phosphorylation of IKKβ. Upon stimulation, the IKK complex, largely through IKKβ, phosphorylates members of the inhibitor of κB (IκB) family, such as IκBα and the IκB-like molecule p105, which sequester NF-κB members in the cytoplasm. IκBα associates with dimers of p50 and members of the REL family (RELA or c-REL), whereas p105 associates with p50 or REL (RELA or c-REL). Upon phosphorylation by IKK, IκBα and p105 are degradated in the proteasome, resulting in the nuclear translocation of canonical NF-κB family members, which bind to specific DNA elements, in the form of various dimeric complexes, including RELA-p50, c-REL-p50, and p50-p50. Atypical, IKK-independent pathways of NF-κB induction also provide mechanisms to integrate parallel signaling pathways to increase NF-κB activity, such as hypoxia, UV and genotoxic stress.

 

The non-canonical NF-κB pathway is induced by certain TNF superfamily members, such as CD40L, BAFF and lymphotoxin-β (LT-β), which stimulates the recruitment of TRAF2, TRAF3, cIAP1/2 to the receptor complex. Activated cIAP mediates K48 ubiquitylation and proteasomal degradation of TRAF3, resulting in stabilization and accumulation of the NFκB-inducing kinase (NIK). NIK phosphorylates and activates IKKα, which in turn phosphorylates p100, triggering p100 processing, and leading to the generation of p52 and the nuclear translocation of p52 and RELB[2][3].

 

Reference:

[1]. Oeckinghaus A, et al. The NF-kappaB family of transcription factors and its regulation.Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a000034. 
[2]. Taniguchi K, et al. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018 May;18(5):309-324.
[3]. Perkins ND,et al. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007 Jan;8(1):49-62.

NF-κB Isoform Comparison

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