1. Signaling Pathways
  2. NF-κB
  3. NF-κB

NF-κB

Nuclear factor-κB; Nuclear factor-kappaB

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.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-14928A
    Lobeglitazone sulfate
    Inhibitor 99.63%
    Lobeglitazone sulfate is a new type of thiazolidinedione. Lobeglitazone sulfate is the orally active agonist for PPAR with EC50 of 137.4 nM and 546.3 nM for PPARγ and PPARα. Lobeglitazone sulfate is the inhibitor for ERK/JNK/Smad/NF-κB signaling pathway. Lobeglitazone sulfate exhibits anti-inflammatory, anti-diabetic, anti-fibrotic and anti-atherosclerotic properties.
    Lobeglitazone sulfate
  • HY-113416AS
    Dehydroepiandrosterone sulfate-d6 sodium dihydrate
    Inhibitor 98.00%
    Dehydroepiandrosterone sulfate sodium dihydrate-d6 sodium dihydrate is the deuterium labeled Dehydroepiandrosterone sulfate sodium dihydrate. Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) sodium dihydrate is a neurosteroid and the main secretion product of the adrenal gland. Dehydroepiandrosterone sulfate sodium dihydrate has both non-competitive antagonist activity of GABAA receptor and agonist activity of σ1 receptor. Dehydroepiandrosterone sulfate sodium dihydrate 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 sodium dihydrate 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 sodium dihydrate may also be a biomarker for cardiovascular disease mortality, and its concentration is independently and negatively correlated with mortality.
    Dehydroepiandrosterone sulfate-d<sub>6</sub> sodium dihydrate
  • HY-15027S1
    5-Aminosalicylic acid-d3
    99.38%
    5-Aminosalicylic acid-d3 is the deuterium labeled 5-Aminosalicylic Acid. 5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB[1][2][3][4].
    5-Aminosalicylic acid-d<sub>3</sub>
  • HY-W014223
    2,4′-Dihydroxybenzophenone
    Inhibitor 98.00%
    2,4′-Dihydroxybenzophenone (Ultraviolet absorber UV-0) occupies the hydrophobic pocket of MD2 and blocks the dimerization of TLR4. 2,4′-Dihydroxybenzophenone inhibits the LPS induced mtROS production, and LPS induced inflammatory response by downregulating pro-inflammatory mediators and decreasing the expression of MyD88, p-IRAK4, and NF-κB. 2,4′-Dihydroxybenzophenone is also a UV absorber.
    2,4′-Dihydroxybenzophenone
  • HY-112433A
    (S)-NIK SMI1
    Control 99.28%
    (S)-NIK SMI1 is the isomer of NIK SMI1 (HY-112433), and can be used as an experimental control. 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.
    (S)-NIK SMI1
  • HY-112433A
    (S)-NIK SMI1
    Inhibitor 99.28%
    (S)-NIK SMI1 is the isomer of NIK SMI1 (HY-112433), and can be used as an experimental control. 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.
    (S)-NIK SMI1
  • HY-N6893
    Ergolide
    Inhibitor 99.75%
    Ergolide is a sesquiterpene lactone isolated from the dried flowers of Inula Britannica. Ergolide inhibits inducible nitric oxide synthase and cyclo-oxygenase-2 expression in RAW 264.7 macrophages through the inactivation of NF-κB.
    Ergolide
  • HY-N2205
    Esculentoside H
    Inhibitor 98.73%
    Esculentoside H (EsH) is a saponin isolated from the root extract of perennial plant Phytolacca esculenta. Esculentoside H (EH) has anti-tumor activity, the mechanism is related to the capacity for TNFrelease. Esculentoside H (EsH) suppresses colon cancer cell migration through blockage of the JNK1/2 and NF-κB signaling-mediated matrix metalloproteinases-9 (MMP-9) expression.
    Esculentoside H
  • HY-W011849
    Phenyl β-D-glucopyranoside
    Inhibitor 99.85%
    Phenyl β-D-glucopyranoside has anti-cancer and anti-inflammatory activities. Phenyl β-D-glucopyranoside inhibits nitric oxide (NO) production, and the expression of iNOS and COX-2. Phenyl β-D-glucopyranoside also inhibits the nuclear translocation of NF-κB.
    Phenyl β-D-glucopyranoside
  • HY-N1196
    Suberosin
    Inhibitor 99.84%
    Suberosin, isolated from Plumbago zeylanica, exhibits anti-inflammatory and anticoagulant activity. Suberosin suppresses PHA-induced PBMC proliferation and arrested cell cycle progression from the G1 transition to the S phase through the modulation of the transcription factors NF-AT and NF-κB.
    Suberosin
  • HY-157793
    SMU-L11
    Activator 99.64%
    SMU-L11 is a specific TLR7 agonist (EC50=0.024 μM), which recruits MyD88 adapter protein and activates downstream NF-κB and MAPK signaling pathways. In murine models, SMU-L11 significantly enhances immune cell activation and promotes the proliferation of CD4+ T and CD8+ T cells, thereby directly killing tumor cells and inhibiting tumor growth. SMU-L11 can be used for cancer research, and also has the potential for studying immune system diseases.
    SMU-L11
  • HY-W001925
    7-Methoxy-1-tetralone
    Inhibitor 99.93%
    7-Methoxy-1-tetralone is a potent antitumor agent. 7-Methoxy-1-tetralone inhibits cancer cell proliferation and migration, and induces hepatocellular carcinoma cell (HCC) apoptosis. 7-Methoxy-1-tetralone decreased the protein levels of NF-κB, matrix metallopeptidase 2 (MMP2)/MMP9, and p-AKT. 7-Methoxy-1-tetralone showed antitumor activity in nude mice and had no effect on body weight and liver, spleen and organ index.
    7-Methoxy-1-tetralone
  • HY-N0290R
    Mangiferin (Standard)
    Inhibitor
    Mangiferin (Standard) is the analytical standard of Mangiferin. This product is intended for research and analytical applications. 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 (Standard)
  • HY-N2303
    Eriocalyxin B
    Inhibitor 99.93%
    Eriocalyxin B is a diterpenoid compound that can be isolated from Chinese herb Isodon eriocalyx. Eriocalyxin B exhibits multiple activities, such as anti-cancer, anti-inflammatory, and inhibition of adipogenesis. Eriocalyxin B is capable of inducing apoptosis and autophagy in tumor cells. Eriocalyxin B can be used in the research of cancers, autoimmune diseases, and other conditions.
    Eriocalyxin B
  • HY-N9942
    Physalin A
    Inhibitor 99.22%
    Physalin A is a biologically active withanolide. Physalin A shows anti-inflammatory, antifibrotic and ameliorative effects on autophagy in models of disc degeneration. Physalin A has antitumor activity and can induce apoptosis, ROS production and G2/M phase cell cycle arrest. Besides. Physalin A can significantly increase the activity of quinone reductase and increase the expression of detoxifying enzymesc.
    Physalin A
  • HY-N11004
    Erinacine C
    Inhibitor 98.61%
    Erinacine C is the inhibitor for NF-κB signaling pathway and the activator for Nrf2 signaling pathway. Erinacine C exhibits antioxidant, neuroprotective and anti-inflammatory effects.
    Erinacine C
  • HY-113416R
    Dehydroepiandrosterone sulfate (Standard)
    Inhibitor
    Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) (Standard) is the analytical standard of Dehydroepiandrosterone sulfate (HY-113416). This product is intended for research and analytical applications. 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 (Standard)
  • HY-W011398
    Linoleate sodium
    99.88%
    Linoleate sodium is an orally active IL8 regulator via the JNK and NF-κB pathway. Linoleate sodium can change the composition of fatty acids and the production of metabolites in cells. Linoleate sodium has anti-inflammatory, immune-regulating, and tumor cell growth-affecting activities.
    Linoleate sodium
  • HY-B0185AS
    Lidocaine-d10 hydrochloride
    Inhibitor 99.79%
    Lidocaine-d10 (hydrochloride) is the deuterium labeled Lidocaine hydrochloride. Lidocaine hydrochloride (Lignocaine hydrochloride) inhibits sodium channels involving complex voltage and using dependence[1]. Lidocaine hydrochloride decreases growth, migration and invasion of gastric carcinoma cells via up-regulating miR-145 expression and further inactivation of MEK/ERK and NF-κB signaling pathways. Lidocaine hydrochloride, an amide derivative, has the potential for the research of the ventricular arrhythmia[2].
    Lidocaine-d<sub>10</sub> hydrochloride
  • HY-137315
    TML-6
    Inhibitor 99.01%
    TML-6, an orally active curcumin derivative, inhibits the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ). TML-6 can upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-oxidative Nrf2 gene. TML-6 has the potential for Alzheimer’s disease (AD) research.
    TML-6
Cat. No. Product Name / Synonyms Application Reactivity

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.

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