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-N11775
    Eudebeiolide B
    		Inhibitor
    Eudebeiolide B is a compound that can be isolated from Salvia plebeia R. Br. Eudebeiolide B inhibits osteoclastogenesis by regulating RANKL-induced NF-κB, c-Fos and calcium signaling. Eudebeiolide B can be used for osteoclast-related diseases research.
    Eudebeiolide B
  • HY-175037
    DNH28
    		Inhibitor
    DNH28 is a potent NF-κB and MAPK inhibitor with an IC50 of 0.93 μM against HepG2 cells. DNH28 promotes apoptosis by down-regulating the expression of Bcl-2, up-regulating the expression of BAX and Cleaved-caspase-3. DNH28 blocks the cell cycle and inhibits migration. DNH28 can be used for the study of hepatocellular carcinoma (HCC).
    DNH28
  • HY-124281
    9(R)-PAHSA
    		Inhibitor
    9(R)-PAHSA is a R-enantiomer of 9-PAHSA. 9-PAHSA is an orally available anti-inflammatory lipid that lowers blood sugar and reduces inflammation.
    9(R)-PAHSA
  • HY-137315S
    TML-6-d3
    TML-6-d3 is the deuterium labeled TML-6. TML-6, an orally active curcumin derivative, inhibits the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ). TML-6 can upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-
    TML-6-d<sub>3</sub>
  • HY-N8719
    Pratol
    		Inhibitor
    Pratol is a potent inhibitor of NF-κB. Pratol significantly reduces NO and prostaglandin PGE2 production without any cytotoxic in LPS-stimulated RAW 264.7 cells. Pratol reduces proinflammatory cytokines. Pratol can be used in study inflammatory diseases and cancer.
    Pratol
  • HY-159144
    Anti-inflammatory agent 91
    		Inhibitor
    Anti-inflammatory agent 91 (Compound 4o) is an anti-inflammatory agent that can reduce inflammatory cytokines by inhibiting the STAT3 and NF-κB signaling pathways. Anti-inflammatory agent 91 can be used in research to improve skin inflammation associated with psoriasis.
    Anti-inflammatory agent 91
  • HY-RS11826
    RELA Human Pre-designed siRNA Set A
    		Inhibitor

    RELA Human Pre-designed siRNA Set A contains three designed siRNAs for RELA gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    RELA Human Pre-designed siRNA Set A
  • HY-149331
    TNF-α-IN-11
    		Inhibitor
    TNF-α-IN-11 (Compound 10) is a TNF-α inhibitor with a KD value of 12.06 μM. TNF-α-IN-11 binds to TNF-α and blocks the activation of TNF-α-trigged caspase and NF-κB signaling pathway. TNF-α-IN-11 inhibits the phosphorylation of IκBα, as well as the nuclear translocation of NF κB p65. TNF-α-IN-11 can be used for research of TNF-α-mediated autoimmune diseases.
    TNF-α-IN-11
  • HY-168070
    COX-2-IN-48
    		Inhibitor
    COX-2-IN-48 (5-25), a COX-2 inhibitor with an IC50 of 51.7 nM for human COX-2, exerts anti-inflammatory and analgesic effects in various rodent models by inhibiting NF-κB pathway. COX-2-IN-48 (5-25) inhibits the degradation of IκB, the phosphorylation and nuclear translocation of NF-κB p65, and the expression of COX-2 and iNOS.
    COX-2-IN-48
  • HY-175270
    MAGL-IN-22
    		Inhibitor
    MAGL-IN-22 (Compound 40) is a reversible, competitive, selective and BBB-penetrable MAGL inhibitor with an IC50 of 0.34  μM for hMAGL. MAGL-IN-22 has significant antioxidant and anti-inflammatory activity, and activates the Nrf2 pathway and significantly inhibits NFκB-mediated inflammation, without inducing cytotoxic effects. MAGL-IN-22 can be used for neurodegenerative diseases, chronic pain and cancers research.
    MAGL-IN-22
  • HY-N0044R
    Ginsenoside Re (Standard)
    		Inhibitor
    Ginsenoside Re (Standard) is the analytical standard of Ginsenoside Re. This product is intended for research and analytical applications. Ginsenoside Re (Ginsenoside B2) is an extract from Panax notoginseng. Ginsenoside Re decreases the β-amyloid protein (Aβ). Ginsenoside Re plays a role in antiinflammation through inhibition of JNK and NF-κB.
    Ginsenoside Re (Standard)
  • HY-P11115
    CIGB-552
    		Inhibitor
    CIGB-552 is a cell-penetrating peptide with anti-tumor properties with the IC50 of 23 μM in H460 cells. CIGB-552 can increase the level of protein COMMD1. CIGB-552 significantly inhibits the NF-κB signaling pathway. CIGB-552 can promote apoptosis of the tumor cells. CIGB-552 can induce the accumulation of reactive oxygen species (ROS) in tumor cells. CIGB-552 has anti-inflammatory and anti-angiogenic effects. CIGB-552 can be used for the research of the lung cancer and colon cancer.
    CIGB-552
  • HY-N12527
    Hyperelamine A
    Hyperelamine A (compound 5) is a polycyclic polyprenylated acylphloroglucinols (PPAPs). Hyperelamine A exhibits inhibitory activity against LPS-activated NO production in BV-2 cells via TLR-4/NF κB signaling.
    Hyperelamine A
  • HY-B0808A
    Oxaprozin potassium
    		Inhibitor
    Oxaprozin potassium is an orally active and potent COX inhibitor, with IC50 values of 2.2 μM for human platelet COX-1 and and 36 μM for IL-1-stimulated human synovial cell COX-2, respectively. Oxaprozin potassium also inhibits the activation of NF-κB. Oxaprozin potassium induces cell apoptosis. Oxaprozin potassium shows anti-inflammatory activity. Oxaprozin potassium-mediated inhibition of the Akt/IKK/NF-κB pathway contributes to its anti-inflammatory properties.
    Oxaprozin potassium
  • HY-N0375R
    18α-Glycyrrhetinic acid (Standard)
    		Inhibitor
    18α-Glycyrrhetinic acid (Standard) is the analytical standard of 18α-Glycyrrhetinic acid. This product is intended for research and analytical applications. 18α-Glycyrrhetinic acid, a diet-derived compound, is an inhibitor of NF-kB and an activator of proteasome, which serves as pro-longevity and anti-aggregation factor in a multicellular organism. 18α-Glycyrrhetinic acid induces apoptosis.
    18α-Glycyrrhetinic acid (Standard)
  • HY-N9699
    8α-Hydroxyhirsutinolide
    		Inhibitor
    8α-Hydroxyhirsutinolide is a sesquiterpene lactone. 8α-Hydroxyhirsutinolide inhibits TNF-α-induced NF-κB activity (IC50: 1.9 μM) and NO production. 8α-Hydroxyhirsutinolide can be isolated from Vernonia cinerea.
    8α-Hydroxyhirsutinolide
  • HY-N15691
    Tadehaginoside
    Tadehaginoside, a phenylpropanoid glycoside, is a regulator of lipogenesis and glucose consumption. Tadehaginoside has antioxygenic property. Tadehaginoside mediates liver protection against oxidative stress injury and inflammation by regulating Nrf2 and NF-κB signaling pathways in hepatocytes. Tadehaginoside can be used for the study of obesity and diabetes.
    Tadehaginoside
  • HY-170659
    NF-κB-IN-18
    		Inhibitor
    NF-κB-IN-18 (Compound 5k) is an orally active NF-κB inhibitor. NF-κB-IN-18 inhibits phosphorylation of p65. NF-κB-IN-18 exhibits potent anti-inflammatory activity in Xylene-induced ear edema mice.
    NF-κB-IN-18
  • HY-W013507R
    (rac)-Methyl jasmonate (Standard)
    		Inhibitor
    (rac)-Methyl jasmonate (Standard) is the analytical standard of Methyl jasmonate. This product is intended for research and analytical applications. (rac)-Methyl jasmonate is the racemate of Methyl jasmonate (HY-135663). Methyl jasmonate is a phytohormone that regulates the defense response of plants under biotic and biotic stress through jasmonate signaling pathway. Methyl jasmonate inhibits the activation of NF-κB signaling pathway. Methyl jasmonate can promote the mitochondrial ROS production, but also scavenges free radicals and reduces the oxidative stress. Methyl jasmonate exhibits anti-inflammatory, antitumor, anticonvulsant, antinociceptive and sedative activities.
    (rac)-Methyl jasmonate (Standard)
  • HY-163355
    COX-2/15-LOX-IN-5
    		Inhibitor
    COX-2/15-LOX-IN-5 (Compound 4f) is a dual inhibitor of COX-2/15-LOX. COX-2/15-LOX-IN-5 attenuates increased NF-κB activation in RAW 264.7 macrophages mediated by lipopolysaccharide (HY-D1056). COX-2/15-LOX-IN-5 has anti-inflammatory and antioxidant activities.
    COX-2/15-LOX-IN-5
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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