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-146419
    Anti-inflammatory agent 20
    		Inhibitor
    Anti-inflammatory agent 20 (compound 5a) is a potent inhibitor of NO activity. Anti-inflammatory agent 20 shows anti-inflammatory activity. Anti-inflammatory agent 20 suppresses LPS-induced inflammation via inhibiting the activation of NF-κB and MAPK signaling and thereby reducing IL-6, TNF-α, iNOS, and COX-2 upregulation.
    Anti-inflammatory agent 20
  • HY-N2477R
    Taraxerol (Standard)
    		Inhibitor
    Taraxerol (Standard) is the analytical standard of Taraxerol. This product is intended for research and analytical applications. Taraxerol is isolated from Taraxacum mongolicum, and has anti-inflammtory and anti-cancer effects. Taraxerol attenuates acute inlammation through inhibition of NF-κB signaling pathway. Taraxerol induces cell apoptosis.
    Taraxerol (Standard)
  • HY-149472
    Anti-osteoporosis agent-4
    		Inhibitor
    Anti-osteoporosis agent-4 (Compound 11h) inhibits differentiation of primary osteoclasts. Anti-osteoporosis agent-4 attenuates RANKL-induced osteoclastogenesis. Anti-osteoporosis agent-4 inhibits osteoclast formation with an IC50 value of 358.29 nM. Anti-osteoporosis agent-4 inhibits PI3K/AKT and IκBα/NF-κB signaling pathway activation.
    Anti-osteoporosis agent-4
  • HY-N3625
    Coronalolic acid
    		Inhibitor
    Coronalolic acid, extract from the apical bud of Gardenia sootepenesis Hutch, inhibits TNF-α-induced NF-κB activity and NO production.
    Coronalolic acid
  • HY-P10839
    NBD peptide
    		Inhibitor
    NBD peptide inhibits NF-κB signaling pathway through inhibition of the NEMO-IKK complex combination. NBD peptide exhibits anti-inflammatory efficacy through block of pro-inflammatory cytokines production. NBD peptide exhibits immunosuppressive activity through regulation of immune cells. NBD peptide enhances its transmembrane ability by combining with cell-penetrating peptide HIV-TAT.
    NBD peptide
  • HY-P10850
    PIYLGGVFQ
    		Inhibitor
    PIYLGGVFQ is a peptide inhibitor for TNF-α. PIYLGGVFQ inhibits TNF-α-mediated apoptosis, NF-κB nuclear translocation and activation. PIYLGGVFQ exhibits anti-arthritic activity in the CIA mouse model.
    PIYLGGVFQ
  • HY-163778
    ZM600
    		Inhibitor
    ZM600 is a potent and orally active antihepatic fibrosis agent. ZM600 decreases the LPS (HY-D1056) induced protein expression of collagen I, α-SM, p-p65. ZM600 has the potential for the research of liver fibrosis.
    ZM600
  • HY-Y1362R
    Ethyl pyruvate (Standard)
    		Inhibitor
    Ethyl pyruvate (Standard) is the analytical standard of Ethyl pyruvate. This product is intended for research and analytical applications. Ethyl pyruvate is a simple derivative of the endogenous metabolite pyruvate. Ethyl pyruvate is an HMGB1 release inhibitor. Ethyl pyruvate can induce apoptosis by autophagy. Ethyl pyruvate has anti-inflammatory, antioxidant and anti-tumor activity. Ethyl pyruvate can be used in the study of neurodegenerative diseases such as Alzheimer's and Parkinson's disease.
    Ethyl pyruvate (Standard)
  • HY-101200R
    Linsidomine hydrochloride (Standard)
    		Activator
    Linsidomine (hydrochloride) (Standard) is the analytical standard of Linsidomine (hydrochloride). This product is intended for research and analytical applications. Linsidomine hydrochloride (SIN-1 chloride) is a spontaneous ROS/RNS generator and peroxynitrite donor. Linsidomine hydrochloride is a vasodilator and platelet aggregation inhibitor. Linsidomine hydrochloride induces oxidative stress-induced chondrocyte apoptosis and necrosis. Linsidomine hydrochloride inhibits the migration, proliferation and neointima formation of vascular smooth muscle cells by inhibiting the expression of annexin A2. In addition, low doses of Linsidomine hydrochloride shows protective effects on Zn2+ treated nerve cells.
    Linsidomine hydrochloride (Standard)
  • HY-122007
    AM-0561
    		Inhibitor
    AM-0561 is a NIK inhibitor (Ki: 0.3 nM). AM-0561 decreases p52 levels.
    AM-0561
  • HY-N8290R
    Lactupicrin (Standard)
    		Inhibitor
    Lactupicrin (Standard) is the analytical standard of Lactupicrin. This product is intended for research and analytical applications. Lactupicrin (Lactucopicrin) exhibits analgesic, sedative, antimalarial activities and atheroprotective effect. Lactupicrin inhibits acetylcholinesterase (AChE) with an IC50 of 150.3 μM. Lactupicrin is an orally active characteristic bitter sesquiterpene lactone.
    Lactupicrin (Standard)
  • HY-N12735
    Hymenoxin
    		Inhibitor
    Hymenoxin (compound 7) is a dual inhibitor of iNOS and NF-κB with IC50 of 42.7 μM and 85.5 μM respectively. Hymenoxin can inhibit 16% of oxidative stress at a concentration of 125 μg/mL.
    Hymenoxin
  • HY-P1832
    PTD-p65-P1 Peptide
    		Inhibitor
    PTD-p65-P1 Peptide is a potent, selective nuclear transcription factor NF-κB inhibitor and derives from the p65 subunit of NF-κB amino acid residues 271-282, which selectively inhibits NF-κB activation induced by various inflammatory stimulation, down-regulate NF-κB-mediated gene expression and up-regulate apoptosis.
    PTD-p65-P1 Peptide
  • HY-128853R
    Taurodeoxycholate sodium salt (Standard)
    		Inhibitor
    Taurodeoxycholate sodium salt (Standard) is a bile salt (Standard)-related anionic detergent. Taurodeoxycholate sodium salt (Standard) is formed in the liver by conjugation of deoxycholate with Taurine (HY-B0351). Taurodeoxycholate sodium salt (Standard) is used for isolation of membrane proteins including inner mitochondrial membrane proteins. Taurodeoxycholate (TDCA) exhibits anti-inflammatory and neuroprotective effects.
    Taurodeoxycholate sodium salt (Standard)
  • HY-N0220R
    Dauricine (Standard)
    		Inhibitor
    Dauricine (Standard) is the analytical standard of Dauricine. This product is intended for research and analytical applications. 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 (Standard)
  • HY-163775
    Anti-inflammatory agent 88
    		Agonist
    Anti-inflammatory agent 88 (compound 6) is a carbazole derivative with anti-inflammatory activity found in marine Streptomyces. It exerts its anti-inflammatory effect by inhibiting pro-inflammatory factors and enhancing the expression of anti-inflammatory factors in the Myd88/Nf-κB pathway. Anti-inflammatory agent 88 can be used for the development of anti-inflammatory drugs.
    Anti-inflammatory agent 88
  • HY-N3497
    Isochamaejasmin
    		Activator
    Isochamaejasmin is a biflavonoid with anti-cancer, antiplasmodial and insecticidal activities. Isochamaejasmin displays a potent NF-κB (NF-κB) activation activity. Isochamaejasmin could cause DNA damage and induce apoptosis via the mitochondrial pathway in AW1 cells. Isochamaejasmin also has a moderate antiplasmodial activity (IC50 of 7.3 μM for P. falciparum) and relatively low cytotoxicity (CC50 of 29.0 μM).
    Isochamaejasmin
  • HY-N0168AR
    (Rac)-Hesperetin (Standard)
    (Rac)-Hesperetin (Standard) is the analytical standard of (Rac)-Hesperetin. This product is intended for research and analytical applications. (Rac)-Hesperetin is the racemate of Hesperetin. Hesperetin is a natural flavanone that can be found in citrus, and acts as a potent and orally active broad-spectrum inhibitor against human UGT activity. Hesperetin induces apoptosis via p38 MAPK activation. Hesperetin displays a range of bioactivities including antioxidant, anti-inflammatory, and anti-cancer. Hesperetin is found to induce cell-cycle arrest at G2/M phase. Hesperetin can reduce Bcl-2 and enhance BaxM. Hesperetin induces apoptosis through inhibiting NF-κB receptor.
    (Rac)-Hesperetin (Standard)
  • HY-N0119R
    Naringin Dihydrochalcone (Standard)
    		Inhibitor
    Naringin Dihydrochalcone (Standard) is the analytical standard of Naringin Dihydrochalcone. This product is intended for research and analytical applications. Naringin Dihydrochalcone is an artificial sweetener derived from naringin. Naringin is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. Naringin exhibits biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. Naringin suppresses NF-κB signaling pathway.
    Naringin Dihydrochalcone (Standard)
  • HY-N2434R
    [10]-Shogaol (Standard)
    		Inhibitor
    -Shogaol (Standard) is the analytical standard of -Shogaol (HY-N2434). This product is intended for research and analytical applications. [10]-Shogaol is an orally active antioxidant. [10]-Shogaol can be extracted from ginger (Zingiber officinale). [10]-Shogaol1 inhibits COX-2 with an IC50 value of 7.5 μM. [10]-Shogaol inhibits the production of proinflammatory cytokines (IL-1β, IL-6). [10]-Shogaol inhibits NF-κB phosphorylation. [10]-Shogaol has anti-inflammatory effects. [10]-Shogaol has anticancer effects against Docetaxel (HY-B0011)-resistant prostate cancer. [10]-Shogaol exhibits larvicidal activity against L5 larvae of Angiostrongylus cantonensis.
    [10]-Shogaol (Standard)
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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