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-108694
    γ-Tocotrienol
    		Inhibitor 99.73%
    γ-Tocotrienol is an active form of vitamin E. γ-tocotrienol reverses the multidrug resistance (MDR) of breast cancer cells through the signaling pathway of NF-κB and P-gp. γ-Tocotrienol is also a radioprotector agent, can mitigate bone marrow radiation damage during targeted radionuclide treatment.
    γ-Tocotrienol
  • HY-N0390R
    L-Glutamine (Standard)
    		Inhibitor
    L-Glutamine (Standard) is the analytical standard of L-Glutamine (HY-N0390). This product is intended for research and analytical applications. L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na+-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.
    L-Glutamine (Standard)
  • HY-W012977
    3,3-Dimethyl-1-butanol
    		Inhibitor 99.56%
    3,3-Dimethyl-1-butanol (DMB) is an orally active inhibitor of trimethylamine (TMA) and trimethylamine N-oxide (TMAO). 3,3-Dimethyl-1-butanol inhibits the signaling pathway of p65 NF-κB and TGF-β1/Smad3. 3,3-Dimethyl-1-butanol has potential applications in cardiovascular disease (CVD).
    3,3-Dimethyl-1-butanol
  • HY-115385
    Lumichrome
    		Inhibitor 99.84%
    Lumichrome, a photodegradation product of Riboflavin, is an endogenous compound in humans. Lumichrome inhibits human lung cancer cell growth and induces apoptosis via a p53-dependent mechanism. Lumichrom is the inhibitor for AKT/β-catenin signaling pathway.
    Lumichrome
  • HY-W016715
    L-Cysteine hydrochloride hydrate
    		Inhibitor 98.0%
    L-Cysteine hydrochloride hydrate is an orally active and essential amino acid, which acts as a precursor for biologically active molecules such as hydrogen sulphide (H2S), glutathione and taurine. L-Cysteine hydrochloride hydrate regulates CBS/H2S pathway, inhibits NF-κB activation and insulin and ghrelin secretion. L-Cysteine hydrochloride hydrate reduces blood sugar, vascular inflammation markers and appetite. L-Cysteine hydrochloride hydrate induces kidney damage. L-Cysteine hydrochloride hydrate can be used in the study of neurological diseases and diabetes.
    L-Cysteine hydrochloride hydrate
  • HY-N8440
    Gibberellin A4
    		Inhibitor 99.65%
    Gibberellin A4 is a type of bioactive gibberellin. Gibberellin A4 promotes flowering in apple trees. Gibberellin A4 also exhibits anti-NF-κB and antioxidant activities. Gibberellin A4 can be used in the research of periodontal diseases.
    Gibberellin A4
  • HY-13755A
    (R)-Sulforaphane
    		Inhibitor 99.95%
    (R)-Sulforaphane (L-Sulforaphane) is a orally active, potent inducer of the Keap1/Nrf2/ARE pathway, exhibiting antioxidant and anticancer activities. (R)-Sulforaphane primarily functions by upregulating phase II detoxifying enzymes in cells, aiding in the removal of carcinogens and combating oxidative stress. (R)-Sulforaphane is capable of modulating gene expression, influencing various signaling pathways, including Nrf2, NF-κB, and AP-1. (R)-Sulforaphane can be used in studies of tumor biology, antioxidant defense mechanisms, as well as inflammation and immune responses.
    (R)-Sulforaphane
  • HY-N9914
    D-Psicose
    		Inhibitor 99.99%
    D-psicose is an orally active rare sugar. D-psicose inhibits p38-MAPK phosphorylation and MCP-1 expression. D-psicose inhibits the AGEs/RAGE/NF-κB pathway. D-psicose protects pancreatic β-islets, improves hyperglycemia and high-fat diet-induced non-alcoholic fatty liver disease.
    D-Psicose
  • HY-N0763
    Angelicin
    		Inhibitor 99.98%
    Angelicin is a furanocoumarin compound that functions as an inhibitor of NF-κB and MAPK signaling pathways, exhibiting anti-inflammatory, antiviral, and antitumor activities. It suppresses the lytic replication of γ-herpesviruses, such as MHV-68, early during viral infection, potentially inhibiting RTA gene expression (IC50=28.95 μM). Angelicin also mitigates inflammation by inhibiting the phosphorylation and nuclear translocation of NF-κB, and the phosphorylation of p38 and JNK. Furthermore, it induces apoptosis in neuroblastoma cells by downregulating anti-apoptotic proteins like Bcl-2, Bcl-xL, and Mcl-1, while activating caspase-9 and caspase-3.
    Angelicin
  • HY-N0753
    Eupalinolide B
    		Inhibitor 99.48%
    Eupalinolide B is a germ sesquiterpene. Eupalinolide B can be isolated from Eupatorium lindleyanum. Eupalinolide B induces Apoptosis, elevates ROS, promotes Autophagy. regulates GSK-3β/β-catenin, targets UBE2D3 and TAK1, activates ROS-ER-JNK, inhibits NF-κB and MAPKs. Eupalinolide B has anticancer activity against pancreatic cancer and liver cancer. Eupalinolide B relieves rheumatoid arthritis, acute lung injury, periodontitis, depression.
    Eupalinolide B
  • HY-Y1267
    Magnesium sulfate
    		Inhibitor 99.63%
    Magnesium sulfate is a calcium antagonist and a potent L-type calcium channel inhibitor, as well as a tocolytic. Magnesium sulfate has anti-inflammatory, anticonvulsant, vasodilatory, and neuroprotective effects. Magnesium sulfate can be used in the research of diseases such as preeclampsia/eclampsia.
    Magnesium sulfate
  • HY-N0390S2
    L-Glutamine-d5
    		Inhibitor 99.79%
    L-Glutamine-d5 is the deuterium labeled L-Glutamine (HY-N0390). L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na+-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.
    L-Glutamine-d<sub>5</sub>
  • HY-N0847
    Micheliolide
    		Inhibitor 99.77%
    Micheliolide is a sesquiterpene lactone with anti-cancer and anti-inflammatory effects, which is derived from Michelia compressa and Michelia champaca. Micheliolide can attenuate high glucose-stimulated NF-κB activation, IκBα degradation, and the expression of MCP-1, TGF-β1, and FN in mouse mesangial cells. Micheliolide inhibits LPS (HY-D1056)-induced activation of NF-κB and PI3K/Akt/p70S6K pathways to play an anti-inflammatory role. Micheliolide inhibits dextran sodium sulphate (DSS) (HY-116282)-induced inflammatory intestinal disease, colitis-associated cancer and rheumatic arthritis.
    Micheliolide
  • HY-N0694
    Schisantherin A
    		Inhibitor 99.87%
    Schisantherin A is a dibenzocyclooctadiene lignan. Schisantherin A inhibits p65-NF-κB translocation into the nucleus by IκBα degradation.
    Schisantherin A
  • HY-N0436
    Engeletin
    		Inhibitor 99.86%
    Engeletin is a flavanonol glycoside isolated from Smilax glabra Roxb. , inhibits NF-κB signaling-pathway activation, and possesses anti-inflammatory, analgesic, diuresis, detumescence, and antibiosis effects.
    Engeletin
  • HY-P3211
    Nangibotide
    		Inhibitor 98.53%
    Nangibotide (LR12) is a synthetic peptide and TREM-1 receptor inhibitor. Nangibotide inhibits NF-κB and NLRP3 inflammasome activation and reduces the release of pro-inflammatory factors (such as IL-1β, IL-8). Nangibotide inhibits Apoptosis. Nangibotide reduces excessive inflammatory responses and protects tissues (liver, lung) from damage. Nangibotide can be used in the researches for myocardial ischemia-reperfusion injury, septic shock, acute lung injury, osteoarthritis, and acute liver failure.
    Nangibotide
  • HY-N0034
    Arctiin
    		Inhibitor 99.52%
    Arctiin is an orally active inhibitor of NF-κB. Arctiin suppresses cyclin D1 protein expression in human tumor cells. Arctiin also reduces malondialdehyde and pro-in ammatory cytokines levels. Arctiin can used in study glomerulonephritis.
    Arctiin
  • HY-B0766
    Bicyclol
    		Inhibitor 99.91%
    Bicyclol (SY801) is an orally active derivative of the traditional Chinese medicine Schisandra chinensis, which has antiviral, anti-inflammatory, immunomodulatory, antioxidant, anti-steatosis, anti-fibrotic and anti-tumor activities. Bicyclol regulates the expression of heat shock proteins and plays an anti-apoptosis role in hepatocytes. Bicyclol reduces the activation of NF-κB and the levels of inflammatory factors in hepatocytes infected with hepatitis C virus (HCV) by inhibiting the activation of the ROS-MAPK-NF-κB pathway, and prevents ferroptosis in acute liver injury. Bicyclol can change the expression of Mdr-1, GSH/GST and Bcl-2, increase the intracellular concentration of anticancer drugs, and sensitize drug-resistant cells to anticancer drugs. Bicyclol inhibits the proliferation of human malignant hepatoma cells by regulating the PI3K/AKT pathway and the Ras/Raf/MEK/ERK pathway. Bicyclol can be used in the study of chronic hepatitis, acute liver injury, nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma.
    Bicyclol
  • HY-P1098A
    Ac2-26 TFA
    		Inhibitor 98.09%
    Ac2-26 TFA is the N-terminal peptide of annexin 1, and has anti-inflammatory activity. Ac2-26 induces a decrease in IKKβ protein in lysosomes by chaperone-mediated autophagy (CMA). Ac2-26 ameliorates lung ischemia-reperfusion injury. Ac2-26 also inhibits airway inflammation and hyperresponsiveness in an asthma rat model.
    Ac2-26 TFA
  • HY-141550
    BPK-25
    		Inhibitor 99.88%
    BPK-25, an active acrylamide, promotes degradation of nucleosome remodeling and deacetylation (NuRD) complex proteins by a post-translational mechanism involving covalent protein engagement. BPK-25 inhibits TMEM173 activation by the cyclic dinucleotide ligand cGAMP.
    BPK-25
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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