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-W754114
    Nalmefene Sulfate-d3
    Nalmefene Sulfate-d3 is the deuterium labeled Nalmefene (HY-107744). Nalmefene is a BBB-penetrable opioid receptor modulator. Nalmefene is an antagonist of MOR and DOR, and a partial agonist of KOR. Nalmefene has anti-inflammatory and neuroprotective activities. Nalmefene can be used in the research of reducing alcohol-dependent disorders.
    Nalmefene Sulfate-d<sub>3</sub>
  • HY-N0298S
    Stachydrine-d6
    Stachydrine-d6 is a deuterated labeled Stachydrine (HY-N0298). Stachydrine is a major constituent of Chinese herb leonurus heterophyllus sweet used to promote blood circulation and dispel blood stasis. Stachydrine can inhibit the NF-κB signal pathway.
    Stachydrine-d<sub>6</sub>
  • HY-N12507
    Eupenicisirenin C
    		Inhibitor
    Eupenicisirenin C (compound 1) is a sirenin derivative. Eupenicisirenin C has strong NF-κB inhibitory activities. Eupenicisirenin C suppresses effects on cGAS-STING pathway. Eupenicisirenin C inhibits RANKL-induced osteoclast differentiation in bone marrow macrophage cells.
    Eupenicisirenin C
  • HY-173416
    Anti-inflammatory agent 100
    		Inhibitor
    Anti-inflammatory agent 100 (Compound (+)-4S-23) is an anti-inflammatory agent. Anti-inflammatory agent 100 inhibits MAPK and NF-κB signaling, and also inhibits NF-κB pathway by suppressing the phosphorylation of IκB-α and blocking nuclear translocation of phosphorylated p65. Anti-inflammatory agent 100 inhibits NO production (IC50: 0.5 μM) and TNF-α, IL-6, IL-1β secretion.
    Anti-inflammatory agent 100
  • HY-107352S
    Fosfenopril-d7
    Fosfenopril-d7 is deuterium labeled Fosfenopril.
    Fosfenopril-d<sub>7</sub>
  • HY-W042416R
    N,N-Dimethylacetamide (Standard)
    		Inhibitor
    N,N-Dimethylacetamide (Standard) is the analytical standard of N,N-Dimethylacetamide. This product is intended for research and analytical applications. N,N-Dimethylacetamide (DMAc) is an organic solvent with blood-brain transmissibility and an FDA-approved drug excipient. N, N-dimethylacetamide exerts anti-inflammatory activity by inhibiting the NF-κB signaling pathway. N, N-dimethylacetamide can be used in studies of weight gain caused by a high-fat diet and neuroinflammation in Alzheimer's disease.
    N,N-Dimethylacetamide (Standard)
  • HY-N0213R
    Peiminine (Standard)
    Peiminine (Standard) is the analytical standard of Peiminine. This product is intended for research and analytical applications. Peiminine is a compound that can be isolated from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family). Peiminine can induce apoptosis in human hepatocellular carcinoma HepG2 cells through both extrinsic and intrinsic apoptotic pathways. Peiminine has anti-inflammatory, anticancer, anti-osteoporosis, cardioprotective and other activities in many animal models.
    Peiminine (Standard)
  • HY-174339
    Neuroprotective agent 12
    Neuroprotective agent 12 is an orally active and BBB-penetrable neuroprotective agent. Neuroprotective agent 12 has potent neuroprotective effects with robust anti-oxidation and anti-inflammation. Neuroprotective agent 12 significantly inhibits glutamate- and acrolein-induced cell death, reduces PDE4B expression but increases the HO-1, p-CREB and BDNF levels. Neuroprotective agent 12 exhibits potent neuroprotection in traumatic brain injury (TBI) mice model, promising for TBI and other central nervous system diseases.
    Neuroprotective agent 12
  • HY-RS09255
    Nfkb1 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Nfkb1 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Nfkb1 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Nfkb1 Mouse Pre-designed siRNA Set A
  • HY-N6636R
    Valencene (Standard)
    		Inhibitor
    Valencene (Standard) is the analytical standard of Valencene. This product is intended for research and analytical applications. Valencene is a sesquiterpene that can be isolated from Cyperus rotundus. Valencene possesses antiallergic, antimelanogenesis, anti-infammatory, and antioxidant activitivies. Valencene inhibits the exaggerated expression of Th2 chemokines and proinflammatory chemokines through blockade of the NF-κB pathway. Valencene inhibits the production and expression of proinflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW 264.7 cells. Valencene can reduce atopic dermatitis symptoms and recover decreased expression of filaggrin in DNCB-sensitized mouse model.
    Valencene (Standard)
  • HY-W046353R
    2-Methoxycinnamaldehyde (Standard)
    		Inhibitor
    2-Methoxycinnamaldehyde (Standard) is the analytical standard of 2-Methoxycinnamaldehyde. This product is intended for research and analytical applications. 2-Methoxycinnamaldehyde (o-Methoxycinnamaldehyde) is a natural compound that can be isolated from Cinnamomum cassia. 2-Methoxycinnamaldehyde inhibits topoisomerase-I/II and NF-κB signaling pathway, causes mitochondrial dysfunction, induces lysosomal vesiculation, thereby leading to DNA damage and cell apoptosis. 2-Methoxycinnamaldehyde exhibits antitumor effects.
    2-Methoxycinnamaldehyde (Standard)
  • HY-126026
    NF-κB-IN-17
    		Inhibitor
    NF-κB-IN-17 (Zinc5) is a NF-κB inhibitor. NF-κB-IN-17 inhibits TNF-α-induced NF-κB DNA binding activity in C2C12 cells.
    NF-κB-IN-17
  • HY-161520
    Glucocorticoid receptor/NF-κB modulator-1
    		Inhibitor
    Glucocorticoid receptor/NF-κB modulator-1 (Compound 20) is a derivative of ocotillol. Glucocorticoid receptor/NF-κB modulator-1 suppresses the degradation of glucocorticoid receptor (GR) mRNA and GR protein, inhibits the activation of NF-κB signaling pathway. Glucocorticoid receptor/NF-κB modulator-1 downregulates levels of NO, interleukin-6 and tumor necrosis factor-alpha (TNF-α). Glucocorticoid receptor/NF-κB modulator-1 ameliorates sepsis in mouse model.
    Glucocorticoid receptor/NF-κB modulator-1
  • HY-128423AS
    Tylvalosin-d9
    		Inhibitor
    Tylvalosin-d9 (Acetylisovaleryltylo?sin-d9) is the deuterium labeled Tylvalosin (HY-128423A). Tylvalosin is a third-generation macrolide, with anti-inflammatory property. Tylvalosin decreases the levels of IL-8, IL-6, IL-1β, PGE2, TNF-α and NO, and reduces the inflammatory cells recruitment and activation in mouse acute lung injury model.
    Tylvalosin-d<sub>9</sub>
  • HY-N2081R
    Skimmianine (Standard)
    Skimmianine (Standard) is the analytical standard of Skimmianine. This product is intended for research and analytical applications. Skimmianine is an orally active furoquiniline alkaloid present mainly in the Rutaceae family. Skimmianine has analgesic, antispastic, sedative, and anti-inflammatory properties. Skimmianine inhibits acetylcholinesterase (AChE) (IC50 = 8.6 μg/mL). Skimmianine exhibits cytotoxicity against a variety of cancer cell lines and genotoxicity. Skimmianine has antioxidant and anti-inflammatory effects on ischemia-reperfusion (IR) injury. Skimmianine exerts anti-inflammatory effects through activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) pathway. Skimmianine is neuroprotective by targeting the NF-κB activation pathway to prevent neuroinflammation. Skimmianine inhibits the release of histamine, intracellular Ca2+ signaling and protein kinase C signaling.
    Skimmianine (Standard)
  • HY-N0747R
    Oxypeucedanin (Standard)
    		Inhibitor
    Oxypeucedanin (Standard) is a furanocoumarin derivative found in Angelica dahurica. Oxypeucedanin (Standard) is an orally active PI3K/AKT/NF-κB, MAPK, and ROS inhibitor. Oxypeucedanin (Standard) induces cell cycle arrest and apoptosis. Oxypeucedanin (Standard) inhibits hKv1.5 channel currents (IC50: 76 nM). Oxypeucedanin (Standard) exhibits anticancer, anti-inflammatory, antioxidant and antiarrhythmic activities.
    Oxypeucedanin (Standard)
  • HY-172788
    NLRP3-IN-78
    		Inhibitor
    NLRP3-IN-78 (compound 21) is a NLRP3 inhibitor with the inhibition rate of 46.72% in GSDMD-induced pyroptosis at 5 μM. NLRP3-IN-78 binds to the NLRP3 protein and inhibits GSDMD-NT oligomerization. NLRP3-IN-78 also inhibits GSDMD cleavage, and upstream NF-κB signaling, demonstrating its anti-inflammatory activity.
    NLRP3-IN-78
  • HY-175277
    PIM1-IN-8
    		Inhibitor
    PIM1-IN-8 is a PIM1/p65 pathway inhibitor. PIM1-IN-8 suppresses the expression of α-SMA and collagen I in activated fibroblasts and blocks TGF-β induced migration. PIM1-IN-8 alleviates pulmonary fibrosis in a Bleomycin (BLM) (HY-17565A)-induced pulmonary fibrosis mice model. PIM1-IN-8 can be used for the study of idiopathic pulmonary fibrosis (IPF).
    PIM1-IN-8
  • HY-14621R
    Zingerone (Standard)
    		Inhibitor
    Zingerone (Standard) is the analytical standard of Zingerone. This product is intended for research and analytical applications. Zingerone (Vanillylacetone) is a nontoxic methoxyphenol isolated from Zingiber officinale, with potent anti-inflammatory, antidiabetic, antilipolytic, antidiarrhoeic, antispasmodic and anti-tumor properties. Zingerone alleviates oxidative stress and inflammation, down-regulates NF-κB mediated signaling pathways. Zingerone acts as an anti-mitotic agent, and inhibits the growth of neuroblastoma cells.
    Zingerone (Standard)
  • HY-118668
    ABD-350
    ABD-350 is an antiresorptive agent that inhibits osteoclast activity without affecting osteoblast activity and preventing ovariectomy-induced bone loss. ABD-350 inhibits NF-κB ligand-induced inhibitor of NF-κB phosphorylation, leading to osteoclast apoptosis, but has no inhibitory effect on osteoblast function, effectively preventing bone loss in ovariectomized mice, and does not inhibit parathyroid hormone-induced bone formation.
    ABD-350
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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