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-117222
    AM-0216
    		Inhibitor
    AM-0216 is a highly selective NF-κB-inducing kinase (NIK) inhibitor with a Ki value of 2 nM. AM-0216 is promising for research of NF-κB-dependent hematologic malignancies (e.g., multiple myeloma) and autoimmune diseases.
    AM-0216
  • HY-149248
    NF-κB-IN-8
    		Inhibitor
    NF-κB-IN-8 competitively antagonizes LPS binding to MD-2. NF-κB-IN-8 reduces the expression of inflammatory factors by binding to MD-2. NF-κB-IN-8 also inhibits ALP activity. NF-κB-IN-8 can be used for the research of inflammation such as acute lung injury (ALI).
    NF-κB-IN-8
  • HY-157211
    Anti-inflammatory agent 66
    		Inhibitor
    Anti-inflammatory agent 66 (compound 8) is a pterostilbene derivative with anti-inflammatory activity. Anti-inflammatory agent 66 inhibits pro-inflammatory cytokines by blocking the LPS-induced NF-κB/MAPK signaling pathway and effectively alleviates DSS-induced acute colitis in mice.
    Anti-inflammatory agent 66
  • HY-W783478
    Calebin A
    		Inhibitor 98.00%
    Calebin A is a PI3K/Akt/mTOR, MAPK, and NF-κB inhibitor with oral effectiveness. Calebin A can block the autophagy-repressive, inhibiting apoptosis. Calebin A has anti-tumor activity by epigenetic regulation. Calebin A suppresses adipogenesis, modulates thermogenesis, and enriches gut probiotics. Calebin A can be used in research on osteoarthritis, Alzheimer's disease, type 2 diabetes, malignant peripheral nerve sheath tumors, and colorectal cancer.
    Calebin A
  • HY-162641
    AF-45
    		Inhibitor
    AF-45 inhibits IRAK4 and IRAK1, with IC50s of 128 nM and 1765 nM. AF-45 inhibits the release of IL-6 and TNF-α in macrophages, with IC50s of 0.53-1.54 μM and 0.6-2.75 μM. AF-45 is also an inhibitor for NF-κB/MAPK signaling pathway. AF-45 exhibits anti-inflammatory activities against DSS-induced ulcerative colitis and Lipopolysaccharide (HY-D1056)-induced acute lung injury in mouse model. AF-45 exhibits good pharmacokinetic characteristics in rat models.
    AF-45
  • HY-156398
    Anti-inflammatory agent 60
    		Inhibitor
    Anti-inflammatory agent 60(compound 21) inhibitsnitric oxide production, with anIC50value of 12.95 μM.Anti-inflammatory agent 60reducesiNOS,phosphorylated p65, andβ-cateninexpression in a concentration-dependent manner.
    Anti-inflammatory agent 60
  • HY-125911R
    Gossypin (Standard)
    		Inhibitor
    Gossypin (Standard) is the analytical standard of Gossypin. This product is intended for research and analytical applications. Gossypin is an orally active flavone isolated from Hibiscus vitifolius. Gossypin has antioxidant, antiinflammatory, anticancer, anticataract, antidiabetic, and hepatoprotective activities. Gossypin inhibits NF-κB and NF-κB-regulated gene expression. Gossypin inhibits AURKA and RSK2. Gossypin inhibits invasion and induces apoptosis. Gossypin can be used for gastric cancer study.
    Gossypin (Standard)
  • HY-175227
    STAT3/NF-κB-IN-1
    		Inhibitor
    STAT3/NF-κB-IN-1 is a potentSTAT3 and NF-κB inhibitor with IC50s of 5.86 (STAT3) and 4.22 μM (NF-κB) in 4T1 cells. STAT3/NF-κB-IN-1 is able to induce apoptosis via its upregulation on key apoptotic regulators; caspases-3/9, Bax and downregulation of Bcl-2. STAT3/NF-κB-IN-1 exerts considerable anticancer activity against breast cancer cell lines and reduces tumor volume in vivo. STAT3/NF-κB-IN-1 can be used for the study of breast cancer.
    STAT3/NF-κB-IN-1
  • HY-B0513R
    Methylthiouracil (Standard)
    		Inhibitor
    Methylthiouracil (Standard) is the analytical standard of Methylthiouracil. This product is intended for research and analytical applications. Methylthiouracil is an antithyroid agent. Methylthiouracil suppresses the production TNF-α and IL-6, and the activation of NF-κB and ERK1/2.
    Methylthiouracil (Standard)
  • HY-N0392R
    Polygalasaponin F (Standard)
    		Inhibitor
    Polygalasaponin F (Standard) is the analytical standard of Polygalasaponin F. This product is intended for research and analytical applications. Polygalasaponin F is an orally active triterpenoid saponin monomer. Polygalasaponin F downregulates the expression of Bax, p53, caspase-3, NF-κB p65 and MEK1; restores and upregulates the expression of Bcl-2; activates the PI3K/Akt signaling pathway; inhibits the phosphorylation of p38 MAPK, nuclear translocation of NF-κB, TLR4-mediated signaling pathway, mitophagy (Mitophagy) and ROS production; enhances cell viability and suppresses apoptosis (Apoptosis). Polygalasaponin F maintains mitochondrial function, alleviates Ca2+ overload, upregulates pCREB and BDNF, preserves cell viability and inhibits the release of inflammatory cytokines. Polygalasaponin F alleviates lung injury induced by influenza A H1N1 and cerebral ischemia-reperfusion injury. Polygalasaponin F is applicable to researches related to Parkinson's disease, cerebral ischemia, pneumonia induced by influenza A H1N1, stroke and Alzheimer's disease.
    Polygalasaponin F (Standard)
  • HY-107352R
    Fosfenopril (Standard)
    		Inhibitor
    Fosfenopril (Standard) is the analytical standard of Fosfenopril. This product is intended for research and analytical applications. Fosfenopril (Fosinoprilat) is a potent angiotensin converting enzyme (ACE) inhibitor. Fosfenopril alleviates lipopolysaccharide (LPS)-induced inflammation by inhibiting TLR4/NF-κB signaling in monocytes.
    Fosfenopril (Standard)
  • HY-178447
    PPARγ agonist 20
    		Inhibitor
    PPARγ agonist 20 is a potent, orally active PPAR-γ agonist. PPARγ agonist 20 effectively increases antioxidant defenses (SOD, GSH) and reduces lipid peroxidation. PPARγ agonist 20 can upregulate of Pparg, Glut4, and AdipoQ, suppresses of TNF-α, IL-6, and NF-κB p65. PPARγ agonist 20 significantly lowers fasting blood glucose, improving glucose tolerance, and restoring metabolic balance in Streptozotocin (HY-13753)-Nicotinamide (HY-B0150)-induced diabetic rats. PPARγ agonist 20 can be used for the study of type 2 diabetes.
    PPARγ agonist 20
  • HY-174321
    A2073
    		Inhibitor
    A2073 is a flavagline derivative that potently inhibits the proliferation of erythroleukemia cells by causing cell cycle arrest and suppressing the MAPK, NF-κB, and PI3K signaling pathways. A2073 formes stable interactions with cell cycle-related proteins (CDK1, CCNA2, PRIM1). A2073 exhibits significant anti-proliferative activity against tumor cells while maintaining a favorable toxicity profile in a zebrafish xenograft tumor model. A2073 can be used for the study of acute erythroleukemia.
    A2073
  • HY-139717
    IMD-biphenylA
    		Modulator
    IMD-biphenylA is a novel imidazoquinolinone-NF-κB immunomodulator dimer that improves the adjuvanticity of small molecule immune potentiators.
    IMD-biphenylA
  • HY-N0498R
    Nitidine chloride (Standard)
    		Inhibitor
    Nitidine (chloride) (Standard) is the analytical standard of Nitidine (chloride). This product is intended for research and analytical applications. Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway.
    Nitidine chloride (Standard)
  • HY-W995241
    BPD
    		Inhibitor
    BPD is a COX-2 and TAK1-NF-κB inhibitor, with an IC50 of 18.5 μM for COX-2. BPD inhibits the expression of iNOS, TNF-α, IL-6 and IL-1β at the transcriptional level. BPD has anti-inflammatory activity. BPD can inhibit Carrageenan-induced paw oedema and LPS-induced septic death.
    BPD
  • HY-N8593S
    Undecane-d24
    		Inhibitor
    Undecane-d24 is the deuterium labeled 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-d<sub>24</sub>
  • HY-N17850
    5-Hydroxy-6,7-dimethoxyflavone
    		Inhibitor
    5-Hydroxy-6,7-dimethoxyflavone is an orally active inhibitor of ferroptosis (Ferroptosis). 5-Hydroxy-6,7-dimethoxyflavone inhibits H1N1 virus-induced ferroptosis by upregulating the expression of SLC7A11 and GPX4. 5-Hydroxy-6,7-dimethoxyflavone alleviates inflammatory responses and inhibits apoptosis by suppressing the activation of the NF-κB and p38 MAPK signaling pathways. 5-Hydroxy-6,7-dimethoxyflavone can be used in studies related to H1N1 influenza virus infection.
    5-Hydroxy-6,7-dimethoxyflavone
  • HY-N1380S2
    Guaiacol-13C6
    Guaiacol-13C6 is the 13C labeled Guaiacol. Guaiacol, a phenolic compound, inhibits LPS-stimulated COX-2 expression and NF-κB activation. Anti-inflammatory activity.
    Guaiacol-<sup>13</sup>C<sub>6</sub>
  • HY-122778R
    δ-Tocotrienol (Standard)
    		Inhibitor
    δ-Tocotrienol (Standard) is the analytical standard of δ-Tocotrienol. This product is intended for research and analytical applications. δ-Tocotrienol is a Vitamin E in vegetables, fruits, seeds, nuts, grains and oils. Vitamin E has become well known for its role as an antioxidant, in lowering cholesterol and other lipids, as a neuroprotective and anticancer agent, and in cardiovascular disease protection.
    δ-Tocotrienol (Standard)
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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