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-15122
    Sinomenine
    		Inhibitor 99.96%
    Sinomenine, an alkaloid extracted from Sinomenium acutum, is a blocker of the NF-κB activation. Sinomenine also is an activator of μ-opioid receptor.
    Sinomenine
  • HY-114544A
    N-3-oxo-dodecanoyl-L-homoserine lactone
    		Activator 99.88%
    N-3-oxo-dodecanoyl-L-Homoserine lactone (3-oxo-C12-HSL) is a bacterial quorum-sensing signaling molecule produced by P. aeruginosa and strains of the B. cepacia complex.Quorum sensing is a regulatory system used by bacteria for controlling gene expression in response to increasing cell density.N-3-oxo-dodecanoyl-L-Homoserine lactone induces the production of IL-8 in 16HBE human bronchial epithelial cells.
    N-3-oxo-dodecanoyl-L-homoserine lactone
  • HY-P9958
    Denosumab
    		Inhibitor 99.10%
    Denosumab is a human monoclonal antibody that targets the protein RANKL. Denosumab binds to the receptor activator of nuclear factor kappa-B ligand (RANKL) and prevents its binding to the RANK receptor (KD of 0.003 nM for human RANKL). Denosumab promotes proliferation and spermatogenesis. Denosumab prevents bone resorption through inhibition of the NF-κB pathway. Denosumab can be used in bone-related studies.
    Denosumab
  • HY-W050154
    Kojic acid
    		Inhibitor 99.99%
    Kojic acid is a substance produced by Aspergillus oryzae that is orally effective and can also be absorbed transdermally. Kojic acid exhibits various biological activities, including anti-aging, anti-nematode, antimicrobial, antioxidant, and anti-inflammatory effects. Kojic acid is a Tyrosinase inhibitor with an Mushroom Tyrosinase IC50 of 182.7 μM. Kojic acid prevents melanin production by capturing copper ions that bind to the tyrosinase active site, thus inhibiting its activation. Kojic acid also suppresses the NF-κB and p21 signaling pathways in human keratinocytes. Kojic acid derivatives have anticancer activity.
    Kojic acid
  • HY-W042416
    N,N-Dimethylacetamide
    		Inhibitor 99.96%
    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
  • HY-128853
    Taurodeoxycholate sodium
    		Inhibitor 99.80%
    Taurodeoxycholate sodium salt is a bile salt-related anionic detergent. Taurodeoxycholate sodium salt is formed in the liver by conjugation of deoxycholate with Taurine (HY-B0351). Taurodeoxycholate sodium salt is used for isolation of membrane proteins including inner mitochondrial membrane proteins. Taurodeoxycholate (TDCA) exhibits anti-inflammatory and neuroprotective effects.
    Taurodeoxycholate sodium
  • HY-N1913
    Danshensu
    		Inhibitor 99.90%
    Danshensu (Dan shen suan A), an orally active phenolic compound, can induce Nrf2/HO-1 activation and inhibition of NF-κB pathway. Danshensu reduces reactive oxygen species (ROS) production, upregulates antioxidant defense mechanism and inhibits intrinsic apoptotic pathway. Danshensu displays a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97 μM. Danshensu has anti-oxidation, anti-apoptosis, anti-lung inflammatory and has the potential for COVID-19, cardiovascular and cerebrovascular diseases research.
    Danshensu
  • HY-P99444
    Astegolimab
    		99.00%
    Astegolimab (MSTT 1041A; RG 6149) is a human IgG2 monoclonal antibody. Astegolimab blocks IL-33 signaling by targeting the IL-33 receptor ST2. Astegolimab reduces p53 expression, mitigates IL33-upregulated SASP factors such as IL1α, IL6 and MCP1. Astegolimab mitigates IL33-increased p-p65/p65 ratio. Astegolimab blocks CM-induced neutrophil extracellular trap (NET) formation. Astegolimab is used in chronic obstructive pulmonary disease (COPD) and myocardial research.
    Astegolimab
  • HY-N0290
    Mangiferin
    		Inhibitor 99.92%
    Mangiferin is a Nrf2 activator. Mangiferin suppresses nuclear translocation of the NF-κB subunits p65 and p50. Mangiferin exhibits antioxidant, antidiabetic, antihyperuricemic, antiviral, anticancer and antiinflammatory activities.
    Mangiferin
  • HY-N0890
    Tubeimoside I
    		Inhibitor 99.96%
    Tubeimoside I is an orally active HSPD1 inhibitor. Tubeimoside I inhibits NF-κB, MAPK, as well as regulates eNOS-VEGF. Tubeimoside I induces cytoprotective Autophagy via an Akt-mediated pathway. Tubeimoside I inhibits proinflammatory cytokine (IL-6 and IL-1β) production. Tubeimoside I exhibits anti-inflammatory activities. Tubeimoside I promotes angiogenesis and improves sepsis symptoms. Tubeimoside I is used in the research of inflammatory diseases, various cancers, sepsis and ischemic diseases.
    Tubeimoside I
  • HY-N0629
    Maslinic acid
    		Inhibitor 99.87%
    Maslinic acid can inhibit the DNA-binding activity of NF-κB p65 and abolish the phosphorylation of IκB-α, which is required for p65 activation.
    Maslinic acid
  • HY-N0029
    Forsythoside B
    		99.90%
    Forsythoside B is a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, a Chinese folk medicinal plant for treating inflammatory diseases and promoting blood circulation. Forsythoside B could inhibit TNF-alpha, IL-6, IκB and modulate NF-κB.
    Forsythoside B
  • HY-120501
    B022
    		Inhibitor 99.27%
    B022 is a potent and selective NF-κB-inducing kinase (NIK) inhibitor (Ki of 4.2 nM; IC50=15.1 nM). B022 protects liver from toxin-induced inflammation, oxidative stress, and injury. B022 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    B022
  • HY-126397
    MnTBAP chloride
    		Inhibitor 98.0%
    MnTBAP chloride is a superoxide dismutase (SOD) mimetic and peroxynitrite scavenger. MnTBAP chloride is a manganic porphyrin complex and has anti-oxidative property. MnTBAP chloride mediates anti-inflammatory effects through upregulation of BMPR-II and inhibition of the NFκB signaling. MnTBAP chloride has the potential for the fibrotic response in chronic kidney diseases (CKDs) research.
    MnTBAP chloride
  • HY-112433
    NIK SMI1
    		Inhibitor 99.92%
    NIK SMI1 is a potent, selective NF-κB inducing kinase (NIK) inhibitor, which inhibits NIK-catalyzed hydrolysis of ATP to ADP with IC50 of 0.23±0.17 nM. NIK SMI1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    NIK SMI1
  • HY-135317
    Emavusertib
    		Inhibitor 99.97%
    Emavusertib is an orally active inhibitor for IRAK4 (IC50=57 nM) and FLT3. Emavusertib inhibits NF-κB and MyD88 signaling pathways, reduces the generation of pro-inflammatory cytokines like IL-6 and IL-10, thereby exhibiting anti-inflammatory and anti-proliferative activities against cancer cells, leading to cell apoptosis. Emavusertib exhibits antitumor activity in mouse model
    Emavusertib
  • HY-N0250
    Saikosaponin D
    		Inhibitor 99.81%
    Saikosaponin D is a triterpene saponin isolated from Bupleurum, with anti-inflammatory, anti-bacterial, anti-tumor, and anti-allergic activities; Saikosaponin D inhibits selectin, STAT3 and NF-kB and activates estrogen receptor-β.
    Saikosaponin D
  • HY-N0441
    Neferine
    		Inhibitor 99.92%
    Neferine is a major bisbenzylisoquinline alkaloid. Neferine strongly inhibits NF-κB activation.
    Neferine
  • HY-N0587
    Demethylzeylasteral
    		Inhibitor 99.92%
    Demethylzeylasteral is an orally active triterpenoid compound isolated from Tripterygium wilfordii, which has functions such as anti-inflammatory, anti-tumor, anti fertility, estrogen metabolism regulation, immune suppression, and immune system regulation [1][2].
    Demethylzeylasteral
  • HY-113416
    Dehydroepiandrosterone sulfate
    		Inhibitor 99.93%
    Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) is a neurosteroid and the main secretion product of the adrenal gland. Dehydroepiandrosterone sulfate has both non-competitive antagonist activity of GABAA receptor and agonist activity of σ1 receptor. Dehydroepiandrosterone sulfate can partially penetrate the blood-brain barrier, inhibit GABAA receptor-mediated chloride influx, enhance NMDA receptor activity through σ1 receptors, exert anti-inflammatory, anti-glucocorticoid and antidepressant effects, and increase convulsive sensitivity. Dehydroepiandrosterone sulfate participates in neuroprotection, neurite growth regulation and catecholamine secretion regulation, and can be used in the study of depression, post-traumatic stress disorder (PTSD), Alzheimer's disease, etc. Dehydroepiandrosterone sulfate may also be a biomarker for cardiovascular disease mortality, and its concentration is independently and negatively correlated with mortality.
    Dehydroepiandrosterone sulfate
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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