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-N2098R
    Obtusifolin (Standard)
    		Inhibitor
    Obtusifolin (Standard) is the analytical standard of Obtusifolin. This product is intended for research and analytical applications. Obtusifolin, isolated from the seeds of Cassia obtusifolia, regulates the gene expression and production of MUC5AC mucin in airway epithelial cells via inhibiting NF-kB pathway. Obtusifolin suppresses phthalate esters-induced breast cancer bone metastasis by targeting parathyroid hormone-related protein.
    Obtusifolin (Standard)
  • HY-120269
    CAY10512
    		Inhibitor
    CAY10512 is a NF-κB inhibitor. CAY10512 can suppress the upregulation of NF-κB-sensitive proinflammatory miRNAs (miRNA-9, miRNA-125b, miRNA-146a, miRNA-155) in cerebrospinal fluid and extracellular fluid. CAY10512 significantly reduces the release of pro-inflammatory cytokines (such as TNF-α, MCP-1, IL-8, IL-6). CAY10512 can be used for researchs on neuroinflammation, islet transplantation and microRNA regulation.
    CAY10512
  • HY-181014
    Glucocorticoid receptor modulator 5
    		Inhibitor
    Glucocorticoid receptor modulator 5 (Compound D8) is a selective, orally active Glucocorticoid receptor modulator. Glucocorticoid receptor modulator 5 shows extremely high transrepression activity (TRNF-κB IC50 = 0.0009 μM, TRAP-1 IC50 = 0.0005 μM). Glucocorticoid receptor modulator 5 exerts its anti-inflammatory activity by interacting directly with the Glucocorticoid receptor signaling pathway. Glucocorticoid receptor modulator 5 significantly alleviates dermatitis and autoimmune hepatitis.
    Glucocorticoid receptor modulator 5
  • HY-D0162R
    Malachite green hemioxalate (Standard)
    		Inhibitor
    Malachite green hemioxalate (Standard) is the analytical standard of Malachite green hemioxalate (HY-D0162). This product is intended for research and analytical applications. Malachite green hemioxalate is a triphenylmethane dye which can be used to detect the release of phosphate in enzymatic reactions. Malachite green hemioxalate has antimicrobial activity, which is attributed to inhibition of intracellular enzymes, intercalation into DNA, and/or interaction with cellular membranes. Malachite green hemioxalate is also a potent and selective inhibitor of IKBKE, and inhibits its downstream targets such as IκBα, p65 and IRF3. Malachite green hemioxalate exhibits antitumor activity in vitro and in vivo.
    Malachite green hemioxalate (Standard)
  • HY-126389A
    Chitin, from shrimp shells (powder)
    Chitin, from shrimp shells (powder) is a long-chain polymer of N-acetylglucosamine with β-(1-4) linkages. Chitin, from shrimp shells (powder) is found in the exoskeleton of crabs. Chitin, from shrimp shells (powder) inhibits the activation of NF-κB p65, alters the translocation of NF-κB p65 to the nucleus, and interacts with the cell wall of Candida species. Chitin, from shrimp shells (powder) exerts antifungal and anti-inflammatory effects. Chitin, from shrimp shells (powder) can be used in the research of gastric ulcer and candidiasis.
    Chitin, from shrimp shells (powder)
  • HY-116678
    Cloricromen
    		Inhibitor
    Cloricromen (Cloricromene) is an orally active platelet inhibitor. Cloricromen inhibits thromboxane B2 release, β-thromboglobulin, and thrombus formation. Cloricromen inhibits LPS (HY-D1056)-induced NF-κB activation, oxidative activity, and TNF-α expression. Cloricromen exhibits protective activity in animal models of shock and peripheral ischaemia. Cloricromen can be used for the research of myocardial ischaemia/reperfusion injury, and ischaemic cerebrovascular disease.
    Cloricromen
  • HY-B0531S
    Triflusal-d3
    		Inhibitor
    Triflusal-d3 is deuterium labeled Triflusal (HY-B0531). Triflusal is an orally bioavailable, blood-brain barrier-permeable dual Cyclooxygenase-1 (COX-1)/cAMP phosphodiesterase inhibitor. Triflusal inhibits platelet aggregation, NF-κB activation, iNOS activity, and prostaglandin synthesis in ischaemic tissue. Triflusal stimulates neutrophil nitric oxide production, eNOS protein expression, and cNOS activity. Triflusal alleviates cerebral ischemic injury in rats and ameliorates pathological lesions and related gene expression in transgenic Alzheimer’s disease models. Triflusal can be used for the research of thromboembolic/ischemic cardiovascular and cerebrovascular diseases, and Alzheimer’s disease.
    Triflusal-d<sub>3</sub>
  • HY-W654377
    Triptolide-d3(major) (>90%)
    Triptolide-d3 (major) (>90%) is the deuterium labeled Triptolide (HY-32735). Triptolide is a diterpenoid triepoxide extracted from the root of Tripterygium wilfordii with immunosuppressive, anti-inflammatory, antiproliferative and antitumour effects. Triptolide is a NF-κB activation inhibitor.
    Triptolide-d<sub>3</sub>(major) (>90%)
  • HY-124557
    Mahanimbine
    		Inhibitor
    Mahanimbine is an orally active alkaloid from Murraya koenigii. Mahanimbine inhibits progression of high-fat diet (HFD)-induced metabolic complications in mice.
    Mahanimbine
  • HY-N10458
    Asperbisabolane L
    		Inhibitor
    Asperbisabolane L, a sesquiterpenoid, exerts the anti-inflammatory activity by inhibiting the NF-κB-activated pathway. Asperbisabolane L inhibits the translocation of NF-κB from cytoplasm to the nucleus. Asperbisabolane L also inhibits NO production in LPS-activated BV-2 microglia cells.
    Asperbisabolane L
  • HY-126047B
    (R)-(+)-Anatabine
    		Inhibitor
    (R)-(+)-Anatabine is an less active R-enantiomer of Anatabine. Anatabine is a potent α4β2 nAChR agonist. Anatabine inhibits NF-κB activation lower amyloid-β (Aβ) production by preventing the β-cleavage of amyloid precursor protein (APP). Anatabine has anti-inflammatory effects and has the potential for neurodegenerative disorders treatment.
    (R)-(+)-Anatabine
  • HY-129599
    L-2286
    		Inhibitor
    L-2286 is an orally active PARP-1 inhibitor. L-2286 alleviates carotid artery remodeling, oxidative stress and inflammation in spontaneously hypertensive rats, protects neurons in the dorsal hippocampus, and reduces pyramidal cell loss and gliosis without affecting blood pressure. L-2286 can be used in research related to hypertension.
    L-2286
  • HY-179214
    DEL-C1
    		Inhibitor
    DEL-C1 is a CHI3L1 inhibitor. DEL-C1 can restore the ability to clear Amyloid-β and repair lysosomal function of astrocytes. DEL-C1 can inhibit NF-κB signaling and IL-6 secretion. DEL-C1 can be used for the researches of inflammation and neurological disease, such as Alzheimer's disease.
    DEL-C1
  • HY-172620
    LIB3S0280
    		Inhibitor 99.89%
    LIB3S0280 is a potent TBK1 inhibitor with an IC50 value of 493.9 nM. LIB3S0280 exhibits better anticancer effects in pancreatic cancer cell lines with high TBK1 expression. LIB3S0280 inhibits TBK1 downstream signaling pathways, including PI3K/AKT and NF-κB. LIB3S0280 induces G2/M arrest, apoptosis and cellular senescence. LIB3S0280 can be used for pancreatic ductal adenocarcinoma (PDAC) research.
    LIB3S0280
  • HY-N0191S
    Andrographolide-d
    Andrographolide-d (Andrographis-d) is the deuterium labeled Andrographolide (HY-N0191). Andrographolide is a NF-κB inhibitor, which inhibits NF-κB activation through covalent modification of a cysteine residue on p50 in endothelial cells without affecting IκBα degradation or p50/p65 nuclear translocation. Andrographolide has antiviral effects.
    Andrographolide-d
  • HY-147770
    NF-κB-IN-6
    		Inhibitor
    NF-κB-IN-6 (Compound 3d) is an anti-inflammatory agent through the mechanism of decreasing the protein expressions of iNOS and COX-2 by suppressing NF-κB signaling pathway. NF-κB-IN-6 inhibits NO production in LPS-induced RAW264.7 cells with an IC50 of 23.1 μM.
    NF-κB-IN-6
  • HY-116474R
    Viridicatol (Standard)
    		Inhibitor
    Viridicatol (Standard) is the analytical standard of Viridicatol (HY-116474). This product is intended for research and analytical applications. Viridicatol is a quinolone alkaloid with anti-inflammatory, antibacterial, antifungal, osteogenic and chondrogenic activities. Viridicatol reduces the phosphorylation levels of ERK, JNK, p38 and STAT6; inhibits MMP-2, MMP-9, NF-κB signaling pathway and PTP1B; downregulates genes related to mast cell activation; and binds to SHN3 to activate the Wnt/SHN3 signaling pathway. Viridicatol inhibits the expression of pro-inflammatory mediators and cytokines, and promotes osteogenic/chondrogenic differentiation. Viridicatol can be used in studies related to fibrosarcoma, allergy, bacterial infection, fungal infection and osteoporosis.
    Viridicatol (Standard)
  • HY-163888
    NO-IN-1
    		Inhibitor
    NO-IN-1 (Compound 7a) inhibits the production of NO (IC50 = 3.13 μΜ). NO-IN-1 has anti-inflammatory effects. NO-IN-1 downregulates the expression of COX-2 and iNOS by inhibiting the NF-κB signaling pathway.
    NO-IN-1
  • HY-N18091
    Tovophyllin A
    		Inhibitor
    Tovophyllin A is an orally active xanthonoid compound. Tovophyllin A exerts neuroprotective effects against Parkinson's disease by activating the Akt/GSK3β signaling pathway. Tovophyllin A protects mouse models of liver injury by activating Nrf2. Tovophyllin A exhibits protective anti-inflammatory activity in mouse models of acute lung injury. Tovophyllin A inhibits the activation of NF-κB and subsequent release of pro-inflammatory cytokines. Tovophyllin A reduces apoptotic cell death (Apoptosis). Tovophyllin A has antiplasmodial activity. Tovophyllin A shows cytotoxic activity against lung epithelial cancer cells and breast cancer cells. Tovophyllin A can be used in research related to Parkinson's disease, liver injury, acute lung injury, lung epithelial cancer, and breast cancer.
    Tovophyllin A
  • HY-B1640A
    Ethacrynic acid sodium
    Ethacrynic acid (Etacrynic acid sodium) sodium is a diuretic. Ethacrynic acid sodium is an inhibitor of glutathione S-transferases (GSTs). Ethacrynic acid sodium is a potent inhibitor of NF-kB-signaling pathway, and also modulates leukotriene formation. Ethacrynic acid sodium also inhibits L-type voltage-dependent and store-operated calcium channel, leading to relaxation of airway smooth muscle (ASM) cells. Ethacrynic acid sodium has anti-inflammatory properties that reduces the retinoid-induced ear edema in mice.
    Ethacrynic acid sodium
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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