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-133708
    β-Glucogallin
    		Inhibitor 99.82%
    β-Glucogallin is an orally active and selective aldose reductase (AKR1B1) inhibitor with an IC50 value of 58 μM when using Glyceraldehyde (HY-128748) as AKR1B1 substrate. β-Glucogallin reduces ROS, PDGF, RAGE, and NF-κB. β-Glucogallin increases SOD. β-Glucogallin has antioxidant and hepatoprotective effects. β-Glucogallin can be used in retinal research.
    β-Glucogallin
  • HY-N3021
    D-chiro-Inositol
    		Inhibitor 98.0%
    D-chiro-Inositol is a stereoisomer of inositol that exhibits activities such as improving glucose metabolism, anti-tumor effects, anti-inflammatory properties, and antioxidant activity. D-chiro-Inositol effectively alleviates cholestasis by enhancing bile acid secretion and reducing oxidative stress. D-chiro-Inositol improves insulin resistance, lowers hyperglycemia and circulating insulin levels, reduces serum androgen levels, and ameliorates some metabolic abnormalities associated with X syndrome by mimicking the action of insulin. Additionally, D-chiro-Inositol can induce a reduction in pro-inflammatory factors (such as Nf-κB) and cytokines (such as TNF-α), thereby exerting anti-inflammatory effects. D-chiro-Inositol may be used in the study of liver cirrhosis, breast cancer, type 2 diabetes, and polycystic ovary syndrome.
    D-chiro-Inositol
  • HY-120657
    9-PAHSA
    		Inhibitor 99.88%
    9-PAHSA is an orally active endogenous GPR120 agonist (EC50=18 μM). 9-PAHSA significantly inhibits LPS-induced inflammatory responses by blocking the NF-κB pathway. 9-PAHSA induces adipocyte browning, enhances glucose uptake and reduces lipid accumulation, while improving mitochondrial function and the survival rate of steatotic hepatocytes. In terms of neuroprotection, 9-PAHSA regulates the expression of REST and BDNF in the prefrontal cortex of diabetic mice, and effectively prevents spatial working memory deficits and abnormal social behaviors. 9-PAHSA does not directly regulate insulin secretion or improve systemic insulin sensitivity, and possesses specific anti-inflammatory, metabolic regulatory and neuroprotective properties. 9-PAHSA can be used in the research of diabetes-related cognitive impairment, obesity and non-alcoholic fatty liver disease.
    9-PAHSA
  • HY-N2534
    Karanjin
    		Inhibitor 99.96%
    Karanjin is an orally active furanoflavonoid which can be isolated from several Leguminosae. Karanjin exhibits evident anti-diabetic, anti-cancer, anti-inflammatory, antioxidant, anticolitis, anti-ulcer, anti-Alzheimer properties and multiple insect repellent/insecticidal, acaricide properties, suggesting the potential of Karanjin to be applied to relevant research.
    Karanjin
  • HY-N8211
    Gypenoside L
    		Activator 99.89%
    Gypenoside L is a saponin that can be found in Gynostemma pentaphyllum. Gypenoside L increases the SA-β-galactosidase activity, promotes the production of senescence-associated secretory cytokines. Gypenoside L also can activate p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Gypenoside L exhibits anti-tumor and anti-inflammatory activities.
    Gypenoside L
  • HY-B0612A
    Lercanidipine hydrochloride
    		Inhibitor 99.93%
    Lercanidipine is a third-generation, lipophilic, brain-penetrant, vascular-selective and orally active dihydropyridine-calcium channel blocker with a pIC50 of 7.74 (converts from μM). Lercanidipine has long lasting antihypertensive action as well as reno- and neuro-protective effect. Lercanidipine also shows anti-oxidant, anti-inflammatory and anti-apoptotic properties. Lercanidipine can be used in cardiovascular and neurological research.
    Lercanidipine hydrochloride
  • HY-N0908
    Ginsenoside Rg5
    		Inhibitor 99.88%
    Ginsenoside Rg5 is the main component of Red ginseng and IGF-1R agonist. Ginsenoside Rg5 compets for the binding site of IGF-1R and blocks the binding of IGF-1 to IGF-1R (IC50 about 90 nM). Ginsenoside Rg5 also inhibits the mRNA expression of COX-2 via suppression of the DNA binding activities of NF-κB p65.
    Ginsenoside Rg5
  • HY-B0900
    Anethole
    		Inhibitor 99.81%
    Anethole is a type of orally active aromatic compound that is widely found in nature and used as a flavoring agent. Anethole possesses anticancer, anti-inflammatory, antioxidant, antibacterial, antifungal, anesthetic, estrogenic, central nervous system depressant, hypnotic, insecticidal, and gastroprotective effects. Anethole can be used in the study of oxidative stress-related skin diseases and prostate cancer.
    Anethole
  • HY-N2609
    7,4'-Dihydroxyflavone
    		Inhibitor 99.64%
    7,4'-Dihydroxyflavone (7,4'-DHF) is a flavonoid, which can be isolated from Glycyrrhiza uralensis. 7,4'-Dihydroxyflavone is eotaxin/CCL11 inhibitor and CBR1 inhibitor (IC50=0.28 μM). 7,4'-Dihydroxyflavone has the ability to consistently suppress eotaxin production and prevent dexamethasone (Dex)‐paradoxical adverse effects on eotaxin production. 7,4'-Dihydroxyflavone (7,4'-DHF) inhibits MUC5AC gene expression, mucus production and secretion via regulation of NF-κB, STAT6 and HDAC2.7,4'-Dihydroxyflavone (7,4'-DHF) decreases phorbol 12-myristate 13-acetate (PMA) stimulated NCI-H292 human airway epithelial cell MUC5AC gene expression and mucus production with IC50 value of 1.4 µM.
    7,4'-Dihydroxyflavone
  • HY-N1193
    Sulfuretin
    		Inhibitor 99.36%
    Sulfuretin inhibits the inflammatory response by suppressing the NF-κB pathway. Sulfuretin can be used for the research of allergic airway inflammation. Sulfuretin reduces oxidative stress, platelet aggregation, and mutagenesis. Sulfuretin is a competitive and potent inhibitor of monophenolase and diphenolase activities with the IC50 of 13.64 μM.
    Sulfuretin
  • HY-N0222
    Avicularin
    		Inhibitor 99.80%
    Avicularin is an orally active flavonoid. Avicularin inhibits NF-κB (p65), COX-2 and PPAR-γ activities. Avicularin has anti-inflammatory, anti-infectious anti-allergic, anti-oxidant, hepatoprotective, and anti-tumor activities.
    Avicularin
  • HY-N0257
    Epimedin A
    		Inhibitor 99.43%
    Epimedin A, one of the main flavonoid active components in Herba Epimedii, is orally active. Epimedin A can inhibit osteoclastogenesis, differentiation, and bone resorption. Epimedin A also possesses anti-inflammatory activity. Epimedin A can be used in the research of osteoporosis and inflammatory diseases.
    Epimedin A
  • HY-N0616
    Trifolirhizin
    		98.37%
    Trifolirhizin is a pterocarpan flavonoid found in the roots of Sophora flavescens. Trifolirhizin is a tyrosinase inhibitor with an IC50 value of 506.77 μM. Trifolirhizin reduces intracellular melanin production and modulates multiple signaling pathways including NFκB-MAPK, AMPK/mTOR, PI3K/Akt, MAPK-NFATc1 and EGFR-MAPK. Trifolirhizin targets biological molecules including PTK6 and COX-2, inhibits the activities of hyaluronidase, collagenase and elastase, induces apoptosis, autophagy and cell cycle arrest, and suppresses the proliferation, migration and invasion of cancer cells. Trifolirhizin exerts diverse pharmacological effects including anti-inflammatory, anti-asthmatic, bone-protective, renoprotective, antibacterial, antifungal, hepatoprotective, antiplatelet, estrogenic and wound-healing activities. Trifolirhizin can be used to investigate a broad range of malignant, inflammatory, metabolic and infectious disorders.
    Trifolirhizin
  • HY-W016412
    Coenzyme Q0
    		Inhibitor 99.79%
    Coenzyme Q0 (CoQ0) is a potent, oral active ubiquinone compound can be derived from Antrodia cinnamomea. Coenzyme Q0 induces apoptosis and autophagy, suppresses of HER-2/AKT/mTOR signaling to potentiate the apoptosis and autophagy mechanisms. Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of inflammation and redox imbalance. Coenzyme Q0 has anti-angiogenic activity through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling.
    Coenzyme Q0
  • HY-N1363
    Royal Jelly acid
    		Inhibitor 99.95%
    Royal Jelly Acid ((E)-Queen Bee Acid) is a major fatty acid found in royal jelly with oral bioavailability, exhibiting anti-inflammatory, anticancer, antimalarial, antiprotozoal, and neuroregulatory activities. Royal Jelly Acid can be used for research in various fields, including cancer, infections, immune inflammation, and neurological diseases.
    Royal Jelly acid
  • HY-N0041
    Ginsenoside Rb3
    		Inhibitor 99.87%
    Ginsenoside Rb3 is extracted from steamed Panax ginseng C. A. Meyer. Ginsenoside Rb3 exhibits inhibitory effect on TNFα-induced NF-κB transcriptional activity with an IC50 of 8.2 μM in 293T cell lines. Ginsenoside Rb3 also inhibits the induction of COX-2 and iNOS mRNA.
    Ginsenoside Rb3
  • HY-D0205A
    Carbocisteine
    		Inhibitor 98.0%
    Carbocisteine is an orally active mucolytic agent. Carbocisteine attenuates the phosphorylation of NF-κB p65 and ERK1/2. Carbocisteine modulates Nrf2/HO-1 and NFκB interplay. Carbocisteine inhibits Apoptosis. Carbocisteine is used in chronic obstructive pulmonary disease (COPD) research.
    Carbocisteine
  • HY-N1949
    Homoplantaginin
    		Inhibitor 99.70%
    Homoplantaginin is a flavonoid from a traditional Chinese medicine Salvia plebeia with antiinflammatory and antioxidant properties. Homoplantaginin could inhibit TNF-α and IL-6 mRNA expression, IKKβ and NF-κB phosphorylation.
    Homoplantaginin
  • HY-N0803
    Myrcene,75% (stabilized with BHT)
    		Inhibitor
    Myrcene (β-Myrcene) is a type of aromatic compound that inhibits TNFα and NF-κB activity. Myrcene has anti-invasive action, inhibits cell cycle, and leads to cancer cell apoptosis. Myrcene has strong blood protection effect, anti-inflammation, and anti-inflammatory activity.
    Myrcene,75% (stabilized with BHT)
  • HY-N0440
    Germacrone
    		Inhibitor 99.76%
    Germacrone is a sesquiterpene compound with multiple biological activities. Germacrone inhibits the H1N1 and H3N2 influenza A virus and the influenza B virus. Germacrone blocks the progressionof arthritis by regulating Th1/Th2 balance and inhibiting NF-κB signaling. Germacrone can arrest the cell cycle at G0/G1 and G2/M phases and induce apoptosis in breast cancer cells. Germacrone inhibits 5α-reductase and has anti-androgenic effect. Germacrone has neuroprotective functions and can be used for the study of traumatic brain injury (TBI). Germacrone also has antioxidant activity.
    Germacrone
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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