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-B1773AR
    Sodium propionate (Standard)
    		Inhibitor
    Sodium propionate (Standard) is the analytical standard of Sodium propionate. This product is intended for research and analytical applications. Sodium propionate is an orally active short-chain fatty acid. Sodium propionate can be produced by intestinal bacteria from the metabolism of dietary fiber. Sodium propionate increases PPAR-γ, inhibits NF-κB activation, and reduces COX-2 expression and NO production. Sodium propionate also induces Apoptosis and Autophagy. Sodium propionate reduces HSV-1-induced keratitis. Sodium propionate has anticancer effects against glioblastoma. Sodium propionate exhibits neuroprotective, antioxidant, and anti-inflammatory activities. Sodium propionate can be used in the research of spinal cord injury and Alzheimer's disease.
    Sodium propionate (Standard)
  • HY-139714
    IMD-vanillin
    		Modulator
    IMD-vanillin is a novel imidazoquinolinone-NF-κB immunomodulator dimers.
    IMD-vanillin
  • HY-N12959
    5,4'-Dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone
    		Inhibitor
    5,4'-Dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone (DDR) is an anticancer agent that can be extracted from Indigofera ovata. 5,4'-Dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone can inhibit the PI3K/AKT and NF-кB pathways, inhibit the invasion and migration of cancer cells, and has anticancer activity.
    5,4'-Dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone
  • HY-N10638
    N-Acetyldopamine dimer-2
    		Inhibitor
    N-Acetyldopamine dimer-2 (compound 2) is a N-acetyldopamine dimer that can be isolated from the yellow powder form Periostracum Cicadae with antioxidant and anti-inflammatory activities. N-Acetyldopamine dimer-2 inhibits oxidized low-density lipoprotein (LDL) oxidation, ROS generation, NO production, and NF-κB activity.
    N-Acetyldopamine dimer-2
  • HY-146560
    Xanthine oxidase-IN-6
    		Inhibitor
    Xanthine oxidase-IN-6 (Compound 6c) is a potent, orally active, mixed-type xanthine oxidase (XOD) inhibitor with an IC50 value of 1.37 µM. Xanthine oxidase-IN-6 shows strong anti-hyperuricemia and renal protective activity.
    Xanthine oxidase-IN-6
  • HY-124281A
    9(S)-PAHSA
    		Control
    9(S)-PAHSA is a S-enantiomer of 9-PAHSA. 9-PAHSA is an orally available anti-inflammatory lipid that lowers blood sugar and reduces inflammation.
    9(S)-PAHSA
  • HY-10540
    Sotrastaurin acetate
    		Inhibitor
    Sotrastaurin (AEB071) acetate is a selective, orally active PKC inhibitor. Sotrastaurin acetate inactivates NF-κB by inhibiting PKC α, β, θ, γ subtypes, thereby reducing the transcription levels of immune response-related genes. Sotrastaurin acetate effectively inhibits alloreactive T cell proliferation, conventional T cell activation, as well as the production of pro-inflammatory cytokines and B lymphocytes. Sotrastaurin acetate also maintains the functional and phenotypic stability of regulatory T cells, enhances Foxp3 expression and restores the balance of helper T lymphocytes. Sotrastaurin acetate can prolong the survival time of allografts, and alleviate inflammatory responses and myasthenic symptoms by reducing anti-AChR antibody levels. Sotrastaurin acetate is widely used in studies related to kidney transplantation, psoriasis and myasthenia gravis.
    Sotrastaurin acetate
  • HY-N8263
    Nepetoidin B
    		Modulator
    Nepetoidin B, an anti-inflammatory agent, inhibits inflammation by modulating the NF-κB and Nrf2/HO-1 signaling pathways. Nepetoidin B also has antifungal and antibacterial activity. Nepetoidin B is a natural product that can be obtained from Salvia plebeia R. Br. Nepetoidin B can be used in anti-inflammatory and anti-infectious research.
    Nepetoidin B
  • HY-175850
    GSK-3β-IN-28
    		Inhibitor
    GSK-3β inhibitor 28 is selective and non-competitivea glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 14.82 nM. GSK-3β inhibitor 28 can upregulate the expression level of phosphorylated GSK-3β and downregulate the expression of p-NF-κB, P65, C-myc and Cyclin D1. GSK-3β inhibitor 28 can induce cells apoptosis, G1 phase arrest and inhibit migration. GSK-3β inhibitor 28 can be used for the research of cancer, such as colorectal cancer.
    GSK-3β-IN-28
  • HY-107272
    Chuanbeinone
    		Inhibitor
    Chuanbeinone (22-Epidelavinone) is an orally active alkaloid found in Fritillaria pallidiflora. Chuanbeinone shows cytotoxicity against mutiple cancer cells and can induces apoptosis and S phase arrest. Chuanbeinone downregulates Bcl-2, upregulates Bax, and activates caspase-3. Chuanbeinone exerts anti-inflammatory and antitussive effects by reducing pro-inflammatory cytokine (IL-1β, IL-6 and TNF-α) production and mRNA expression, and inhibiting TRIF-, MyD88-, NF-κB-, and MAPK-dependent signaling pathways. Chuanbeinone inhibits AChE and BChE with IC50 values of 7.7 and 0.7 μM. Chuanbeinone can be used for the researches of lung carcinoma, cough, inflammatory diseases.
    Chuanbeinone
  • HY-116145
    MHY884
    		Inhibitor
    MHY884 is a tyrosinase inhibitor that suppresses UVB-induced activation of NF-κB signaling pathway through the downregulation of oxidative stress. MHY884 suppresses oxidative stress in the melanoma cells and attenuates UVB-induced oxidative stress, resulting in reduced NF-κB activity in irradiated mice. MHY884 is promising for research of UVB-induced skin damage.
    MHY884
  • HY-P1752A
    Urocortin II, human TFA
    		Activator
    Urocortin II, human TFA is a selective endogenous peptide agonist of type-2 corticotropin-releasing factor (CRF2) receptor. Urocortin II, human TFA has an effect of promoting satiet and neuroprotective effect. Urocortin II, human TFA also has bactericidal, antiparasitic and pro-inflammation activity. Urocortin II, human TFA can activate NF-κB pathway and ERK1/2 MAP kinase. Urocortin II, human TFA can reduce pulmonary arterial hypertension and shows cardiac protection effect. Urocortin II, human TFA can be used for the researches of infection, inflammation, metabolic, neurological and cardiovascular disease.
    Urocortin II, human TFA
  • HY-165370
    BMS-791826
    BMS-791826 is a selective glucocorticoid receptor modulator. BMS-791826 effectively binds to glucocorticoid receptors and effectively inhibits AP-1 and NF-κB-dependent reporter. BMS-791826 can be used in the research of inflammatory diseases.
    BMS-791826
  • HY-180336
    LM9
    		Inhibitor
    LM9 is a potent, orally active MyD88 inhibitor. LM9 blocks TLR4/MyD88 binding, MyD88 homodimer formation, and TLR4/MyD88/NF-κB signaling pathway activation. LM9 prevents atherosclerosis by regulating inflammatory responses and oxidative stress in macrophages. LM9 efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy. LM9 can be used for fibrosis and atherosclerosis research.
    LM9
  • HY-RS11831
    Relb Rat Pre-designed siRNA Set A
    		Inhibitor

    Relb Rat Pre-designed siRNA Set A contains three designed siRNAs for Relb gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Relb Rat Pre-designed siRNA Set A
  • HY-N11494
    Dauricumine
    		Inhibitor
    Dauricumine is a chlorinated alkaloid that inhibits NF-κB ligand-induced differentiation of mouse bone marrow-derived macrophages into multinucleated osteoclasts.
    Dauricumine
  • HY-P992354
    FPA154
    		Activator
    FPA154 is a human monoclonal antibody against TNFRSF18/GITR/CD357. FPA154 activates NF-κB via the GITR pathway. FPA154 can be used in solid tumor research. Recommend Isotype Controls: Human IgG1 kappa, Isotype Control (HY-P99001).
    FPA154
  • HY-183573
    PTPRO-IN-1
    		Inhibitor
    PTPRO-IN-1 is a selective, orally active PTPRO inhibitor with an IC50 of 0.16 μM. PTPRO-IN-1 exhibits IC50 values of 2.4 μM, 2.33 μM and 2.13 μM against PTPN22, PTP1B and PTPRT, respectively, and shows almost no inhibitory activity against STEP/SSH2. PTPRO-IN-1 inhibits the TLR4/NF-κB signaling pathway in macrophages, ameliorates colonic pathological conditions and suppresses the secretion of pro-inflammatory cytokines by T cells. PTPRO-IN-1 can be used for the research of inflammatory bowel disease.
    PTPRO-IN-1
  • HY-173129
    Anti-inflammatory agent 97
    Anti-inflammatory agent 97 (Compound 1l), an anti-inflammation agent, can also inhibit oxidative stress. Anti-inflammatory agent 97 can inhibit the colonic shortening and suppress inflammatory symptoms of the colonic tissue in the DSS (HY-116282C)-induced ulcerative colitis mice model. Anti-inflammatory agent 97 can regulate the inflammation-related TLR4/NF-κB signaling pathway and the oxidative stress-related Nrf2/HO-1 signaling pathway.
    Anti-inflammatory agent 97
  • HY-160938
    β-Funaltrexamine
    		Inhibitor
    β-Funaltrexamine (β-FNA) is a blood-brain barrier-permeable, selective and irreversible μ-opioid receptor antagonist with immunomodulatory, anti-inflammatory and neuroprotective activities. β-Funaltrexamine inhibits p38 MAPK and TLR4 signaling by blocking μ-opioid receptors, and reduces the transcriptional activities of NF-κB, AP-1, CREB and Stat. Furthermore, β-Funaltrexamine inhibits iNOS activation and pro-inflammatory microglial polarization, converting microglia to an anti-inflammatory phenotype, thereby downregulating neuroinflammation and ameliorating neuronal degeneration. β-Funaltrexamine is widely applicable to research related to stroke, cerebral ischemia/reperfusion injury and neurodegenerative diseases.
    β-Funaltrexamine
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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