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-N0220
    Dauricine
    		Inhibitor 99.75%
    Dauricine, a bisbenzylisoquinoline alkaloid in Menispermum dauricum, possesses anti-inflammatory activity. Dauricine inhibits cell proliferation and invasion, and induces apoptosis by suppressing NF-κB activation in a dose- and time-dependent manner in colon cancer.
    Dauricine
  • HY-B2123
    Lactose
    		Inhibitor ≥98.0%
    Lactose is a β-galactoside consisting of galactose and glucose residues，the main carbohydrate in mammalian breast milk. Lactose，a macronutrient and an inducer of host innate immune responses，possesses immune modulatory functions.
    Lactose
  • HY-N6949
    Juglone
    		Inhibitor 99.77%
    Juglone (5-hydroxy-1,4-naphthalenedione) is a yellow dye that can be extracted from Juglans regia. Juglone induces apoptosis through the mitochondrial pathway. Juglone has antibacterial and antitumor activity .
    Juglone
  • HY-130603
    DCZ0415
    		Inhibitor 99.81%
    DCZ0415, a potent TRIP13 inhibitor, impairs nonhomologous end joining repair and inhibits NF-κB activity. DCZ0415 induces anti-myeloma activity in vitro, in vivo, and in primary cells derived from drug-resistant myeloma patients.
    DCZ0415
  • HY-N0298
    Stachydrine
    		Inhibitor ≥98.0%
    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
  • HY-N0279
    Cardamonin
    		Inhibitor 98.38%
    Cardamonin can be found from cardamom, and can target various signaling molecules, transcriptional factors, cytokines and enzymes. Cardamonin can inhibit mTOR, NF-κB, Akt, STAT3, Wnt/β-catenin and COX-2. Cardamonin shows anticancer, anti-inflammatory, antimicrobial and antidiabetic activities.
    Cardamonin
  • HY-10454
    Delanzomib
    		Inhibitor ≥98.0%
    Delanzomib (CEP-18770) is a potent and orally active chymotrypsin-like activity of the proteasome inhibitor with an IC50 of 3.8 nM. Delanzomib inhibits NF-κB activity, induces cancer cell apoptotic, and has strong antiangiogenic and anti-cancer activities.
    Delanzomib
  • HY-17403
    Manidipine dihydrochloride
    		Inhibitor 99.84%
    Manidipine dihydrochloride is a third-generation, lipophilic, orally active and highly vasoselective calcium channel antagonist (IC50 = 2.6 nM in guinea-pig ventricular cells) and acts as an antihypertensive agent. Manidipine effectively reduces blood pressure as well as improving insulin sensitivity, renal protection, and antiatherosclerotic activity. Manidipine also exerts anti-inflammatory activity mediated by NF-κB and antiviral activity against many flavivirus and negative-strand RNA viruses through the inhibition of calcium channel. Manidipine is widely applied to research of cardiovascular, metabolic disease and infection.
    Manidipine dihydrochloride
  • HY-N0755
    Rhoifolin
    		Activator 99.25%
    Rhoifolin is a flavone glycoside can be isolated from Rhus succedanea. Rhoifolin has anti-diabetic effect acting through enhanced adiponectin secretion, tyrosine phosphorylation of insulin receptor-β and glucose transporter 4 (GLUT 4) translocation. Rhoifolin has an anti-inflammatory action via multi-level regulation of inflammatory mediators. Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-κB and MAPK pathways. Rhoifolin also has cytotoxic activity against different cancer cell lines.
    Rhoifolin
  • HY-N0498
    Nitidine chloride
    		Inhibitor 99.75%
    Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway, also has anti-inflammatory activity. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway.
    Nitidine chloride
  • HY-N0387
    Rhynchophylline
    		Inhibitor 99.75%
    Rhyncholphylline is an alkaloid compound isolated from Uncaria rhynchophyllum. Rhyncholphylline is an EphA4 inhibitor. It has high biological activity and is widely used in anti-inflammatory, neuroprotective and other research..
    Rhynchophylline
  • HY-P99673
    Itepekimab
    		Inhibitor 99.40%
    Itepekimab (REGN-3500) is an IgG4 monoclonal antibody against IL-33. Itepekimab reduced airway inflammation and related tissue damage in preliminary clinical studies. Itepekimab has potential effects in asthma, chronic obstructive pulmonary disease (COPD), and atopic dermatitis (AD).
    Itepekimab
  • HY-W145499
    Zinc Gluconate
    		Inhibitor 98.2%
    Zinc Gluconate is a zinc supplement in the form of a gluconate salt, which plays a role in various physiological processes such as immune function, wound healing, and olfaction. Zinc Gluconate has a LD50 of 39.6 mg/kg in mice (Tail vein injection). Zinc Gluconate can be used in the research of inflammation, zinc deficiency, colds, cancer, and nutritional supplements.
    Zinc Gluconate
  • HY-N8518
    Malabaricone C
    		Inhibitor 99.61%
    Malabaricone C is an orally active and noncompetitive sphingomyelin synthase (SMS) inhibitor with IC50 values of 3 μM and 1.5 μM for SMS 1 and SMS 2, respectively. Malabaricone C reduces body weight gain, improves glucose tolerance, and decreases lipid accumulation in the liver, showing significant prevention of high fat diet-induced fatty liver in mice. Malabaricone C has anti-inflammatory effects, which is found in the fruits of Myristica cinnamomea King. Malabaricone C is promising for research of obesity and immunological disorders caused due to hyper-activation of T-cells.
    Malabaricone C
  • HY-B0185A
    Lidocaine hydrochloride
    		Inhibitor 99.84%
    Lidocaine hydrochloride (Lignocaine hydrochloride) inhibits sodium channels involving complex voltage and using dependence. 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 is an amide derivative and a agent to treat ventricular arrhythmia and an effective tumor-inhibitor.
    Lidocaine hydrochloride
  • HY-N6727
    Gliotoxin
    		Inhibitor 99.51%
    Gliotoxin is a secondary metabolite, the most abundant mycotoxin secreted by A. fumigatus, inhibits the phagocytosis of macrophages and the immune functions of other immune cells . Gliotoxin inhibits inducible NF-κB activity by preventing IκB degradation, which consequently induces host-cell apoptosis. Gliotoxin activates PKA and increases intracellular cAMP concentration; modulates actin cytoskeleton rearrangement to facilitate A. fumigatus internalization into lung epithelial cells. Gliotoxin is a potent NOTCH2 transactivation inhibitor, can effectively induce apoptosis of chronic lymphocytic leukemia (CLL) cells.
    Gliotoxin
  • HY-126389
    Chitin, from crab carapace (powder)
    		Inhibitor
    Chitin, from crab carapace is a long-chain polymer of N-acetylglucosamine with β-(1-4) linkages. Chitin, from crab carapace is found in the exoskeleton of crabs. Chitin, from crab carapace inhibits the activation of NF-κB p65, alters the translocation of NF-κB p65 to the nucleus, and interacts with the cell wall of Candida species. Chitin, from crab carapace exerts antifungal and anti-inflammatory effects. Chitin, from crab carapace can be used in the research of gastric ulcer and candidiasis.
    Chitin, from crab carapace (powder)
  • HY-116035
    Nimbolide
    		Inhibitor 99.79%
    Nimbolide is a triterpene compound that can be isolated from neem (Azadirachta indica), possesses anticancer and antiproliferative activity. Nimbolide induces tumor cell apoptosis by inhibiting NF-κB and CDK4/CDK6 kinase. Nimbolide suppresses the Wnt, PI3K-Akt, MAPK and JAK-STAT signaling pathways.
    Nimbolide
  • HY-152860
    Darizmetinib
    		Activator 99.94%
    Darizmetinib (HRX-0215) is an orally active, potent and selective inhibitor of mitogen-activated protein kinase kinase 4 (MKK4). Darizmetinib leads to enhancement of the MKK7 and JNK1 signaling pathways, thereby activating the transcription factors ATF2 and ELK1, promoting cell proliferation and liver regeneration. Darizmetinib is promising for research of preventing liver failure after extensive oncological liver resections or transplantation of small liver grafts.
    Darizmetinib
  • HY-N0815
    Resibufogenin
    		Inhibitor 99.93%
    Resibufogenin is an orally active anticancer agent. Resibufogenin can be extracted from toad venom. Resibufogenin blocks signaling pathways such as PI3K/Akt, NF-κB, AP-1, activates GSK-3β, and regulates cyclin D1. Resibufogenin can activate central neurons. Resibufogenin has anti-inflammatory activity. Resibufogenin has anti-tumor effects on a variety of tumors such as multiple myeloma, renal cancer, colorectal cancer, pancreatic cancer, and glioma.
    Resibufogenin
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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