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-N0073
    Sarsasapogenin
    		Inhibitor 99.91%
    Sarsasapogenin is a sapogenin from the Chinese medical herb Anemarrhena asphodeloides Bunge, with antidiabetic, anti-oxidative, anticancer and anti-inflamatory activities.
    Sarsasapogenin
  • HY-N0908
    Ginsenoside Rg5
    		Inhibitor 99.87%
    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-110195
    Smurf1-IN-A01
    		99.81%
    Smurf1-IN-A01 is a Smurf1 inhibitor. Smurf1-IN-A01 has anticancer activity and can be used for the research of osteoporosis and age-related macular degeneration.
    Smurf1-IN-A01
  • HY-N0034
    Arctiin
    		Inhibitor 99.52%
    Arctiin is an orally active inhibitor of NF-κB. Arctiin suppresses cyclin D1 protein expression in human tumor cells. Arctiin also reduces malondialdehyde and pro-in ammatory cytokines levels. Arctiin can used in study glomerulonephritis.
    Arctiin
  • HY-N0716A
    Berberine hemisulfate
    		Inhibitor 99.63%
    Berberine hemisulfate is the hemisulfate form of Berberine (HY-N0716). Berberine hemisulfate is an alkaloid isolated from the Chinese herbal medicine Huanglian. Berberine hemisulfate exhibits anti-inflammatory, antibiobic, antitumor, cardiovascular protective and neuroprotective activity.
    Berberine hemisulfate
  • HY-120371
    CPUY192018
    		Inhibitor 98.99%
    CPUY192018 is a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, with an IC50 of 0.63 µM. CPUY192018 exhibits anti-inflammatory and antioxidant activities. CPUY192018 can activate the Nrf2-dependent antioxidant pathway and inhibit the NF-κB-related inflammatory response. CPUY192018 can be used in the research of inflammation-related diseases.
    CPUY192018
  • HY-N1949
    Homoplantaginin
    		Inhibitor 99.90%
    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-N1404
    Sodium aescinate
    		Inhibitor 99.26%
    Sodium aescinate is a triterpene saponin derived from Aesculus hippocastanum seeds, with anti-inflammatory and antioxidant activities. Sodium aescinate inhibits hepatocellular carcinoma growth by targeting CARMA3/NF-κB pathway.
    Sodium aescinate
  • HY-107574
    TC-E 5003
    		Modulator 98.03%
    TC-E 5003 is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC50 of 1.5 µM against hPRMT1. TC-E 5003 modulates the lipopolysaccharide (LPS) (HY-D1056)-induced AP-1 and NF-κB signaling pathways with anti-inflammatory properties. TC-E 5003 also upregulates the expression of Ucp1 and Fgf21, activates protein kinase A signaling and lipolysis in primary subcutaneous adipocytes from both mouse and humans. TC-E 5003 is promising for research of obesity and associated metabolic disorders, oxidative stress, inflammation and cancers.
    TC-E 5003
  • HY-N1419
    Vaccarin
    		Inhibitor 98.47%
    Vaccarin is an orally active flavonoid glycoside with multiple biological functions. Vaccarin promotes neovascularization by activating AKT and ERK. Vaccarin activates the AMPK signaling pathway to improve insulin resistance and steatosis. Vaccarin is a MAPK, NF-κB, and NFAT inhibitor, effectively blocking RANKL-induced osteoclastogenesis.
    Vaccarin
  • HY-N0738
    Stachydrine hydrochloride
    		Inhibitor ≥98.0%
    Stachydrine hydrochloride is the major active constituent of Leonurus artemisia, which is a potential therapy for cardiovascular diseases. Stachydrine can inhibit the NF-κB signal pathway. Anti-hypertrophic activities.
    Stachydrine hydrochloride
  • HY-N6602
    α-Solanine
    		Inhibitor 99.89%
    α-solanine, a bioactive component and one of the major steroidal glycoalkaloids in Solanum nigrum, has been observed to inhibit growth and induce apoptosis in cancer cells.
    α-Solanine
  • HY-P3042
    Chymostatin
    		Inhibitor ≥99.0%
    Chymostatin is a SARS-CoV-2 Mpro inhibitor. Chymostatin up-regulates endocan and inhibits NF-κBp65 activity. Chymostatin reduces proinflammatory cytokines (IL-1β and IL-6) and HMGB1. Chymostatin shows protective effects against Paraquat-induced acute lung injury. Chymostatin exhibits anticancer activity against lung cancer.
    Chymostatin
  • HY-N8211
    Gypenoside L
    		Activator 99.55%
    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-N4187
    Licochalcone D
    		Inhibitor 99.81%
    Licochalcone D, a flavonoid compound mainly existing in the root of Glycyrrhiza uralensis, is a potent and orally active inhibitor of NF-kappaB (NF-κB) p65. Licochalcone D possesses antioxidant, anti-inflammatory, anti-cancer properties.
    Licochalcone D
  • HY-108039
    Bezisterim
    		Inhibitor
    Bezisterim (HE 3286; NE-3107) is a synthetic derivative of a natural anti-inflammatory steroid, β-AET. Bezisterim is an orally active partial NF-κB inhibitor. HE3286 reduces proinflammatory signals, including IL-6 and matrix metallopeptidase 3. Bezisterim freely penetrates the blood brain barrier in mice. Bezisterim can be used for the research of the ulcerative colitis, arthritis, experimental autoimmune encephalomyelitis. Bezisterim is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    Bezisterim
  • HY-110261
    GS143
    		Inhibitor 99.09%
    GS143 is a selec­tive IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. GS143 sup­presses NF-κB acti­va­tion and tran­scrip­tion of tar­get genes and does not inhibit proteasome activity. GS143 has anti-asthma effect.
    GS143
  • HY-N2464
    Maltotetraose
    		Inhibitor 99.88%
    Maltotetraose can serve as a substrate for enzyme-linked assays to measure amylase activity in biological fluids. Maltotetraose has oral active, and reduces TNF-α-induced inflammatory responses by inhibiting NF-κB activity and decreasing ICAM-1 expression. Maltotetraose also inhibits PDGF-induced vascular smooth muscle cell migration and neovascularization. Additionally, Maltotetraose derivatives can function as probes for detecting bacterial infections by targeting the maltodextrin transporter. With good long-term safety, Maltotetraose holds promise for research in atherosclerosis-related diseases.
    Maltotetraose
  • HY-134240
    L-Threonic acid magnesium
    		Inhibitor ≥99.0%
    L-Threonic acid magnesium (Magnesium L-threonate) is the enantiomer of Threonic acid and the metabolite of vitamin C (HY-B0166). L-Threonic acid magnesium is a magnesium supplementation, that improves the brain magnesium concentration, inhibits the activation of TNF-α/NF-κB signaling pathway. L-Threonic acid magnesium can be used in research of Alzheimer’s disease. L-Threonic acid magnesium is orally active.
    L-Threonic acid magnesium
  • HY-N0694
    Schisantherin A
    		Inhibitor 99.87%
    Schisantherin A is a dibenzocyclooctadiene lignan. Schisantherin A inhibits p65-NF-κB translocation into the nucleus by IκBα degradation.
    Schisantherin A
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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