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-N8593
    Undecane
    Inhibitor 99.66%
    Undecane is a potent cAMP agonist with anti-allergic and anti-inflammatory activities. Undecane inhibits degranulation and the secretion of histamine and TNF-α. Undecane reverses the increased levels of p38 phosphorylation, NF-κB transcriptional activity and target cytokine/chemokine genes, including thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and interleukin-8 (IL-8). Undecane can be used for the study of skin inflammatory disorders, such as atopic dermatitis.
    Undecane
  • HY-N0440R
    Germacrone (Standard)
    Inhibitor
    Germacrone (Standard) is an analytical standard of Gemmacrone (HY-N0440). This product is intended for research and analytical applications. Germacrone (Standard) is a sesquiterpene compound with multiple biological activities. Germacrone (Standard) inhibits the H1N1 and H3N2 influenza A viruses and the influenza B virus. Germacrone (Standard) blocks the progressionof arthritis by regulating Th1/Th2 balance and inhibiting NF-κB signaling. Germacrone (Standard) can arrest the cell cycle at G0/G1 and G2/M phases and induce apoptosis in breast cancer cells. Germacrone (Standard) inhibits 5α-reductase and has anti-androgenic effect. Germacrone (Standard) has neuroprotective functions and can be used for the study of traumatic brain injury (TBI). Germacrone (Standard) also has antioxidant activity.
    Germacrone (Standard)
  • HY-P990124
    Anti-Mouse GITR Antibody (DTA-1)
    Activator 98.47%
    Anti-Mouse GITR Antibody (DTA-1) is a rat derived IgG2b monoclonal agonist antibody targeting mouse GITR. Anti-Mouse GITR Antibody (DTA-1) can activate T cells and B cells to enhance immune response. Anti-Mouse GITR Antibody (DTA-1) selectively enhances Th2 cell effector function through GITR signaling. Anti-Mouse GITR Antibody (DTA-1) may exacerbate allergic reactions. Anti-Mouse GITR Antibody (DTA-1) can be used for researches on cancer and allergic conditions such as colon cancer and allergic asthma. The recommed isotype control of Anti-Mouse GITR Antibody (DTA-1) is Rat IgG2b kappa, Isotype Control (HY-P990682).
    Anti-Mouse GITR Antibody (DTA-1)
  • 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-N0854
    Alisol F
    Inhibitor 99.89%
    Alisol F is a protostane-type triterpenoid with anti-inflammatory and anti-hepatitis B virus activities. Alisol F inhibits LPS (HY-D1056)-induced phosphorylation of ERK, JNK, p38, STAT3 and NF-κB (p65), suppresses the production of NO, IL-6, TNF-α and IL-1β, and also downregulates the levels of iNOS and COX-2. Alisol F reduces the serum alanine aminotransferase and aspartate aminotransferase levels in mice with acute liver injury and ameliorates their liver pathological damage.
    Alisol F
  • HY-15027R
    5-Aminosalicylic Acid (Standard)
    Inhibitor
    5-Aminosalicylic Acid (Standard) is the analytical standard of 5-Aminosalicylic Acid. This product is intended for research and analytical applications. 5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB. 5-Aminosalicylic acid can inhibit the activity of osteopontin (OPN).
    5-Aminosalicylic Acid (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-12286
    PI-1840
    Inhibitor 98.78%
    PI-1840 is a potent and selective chymotrypsin-like (CT-L) inhibitor for with an IC50 value of 27 nM. PI-1840 inhibits cell proliferation and arrest cell cycle at G2/M phase. PI-1840 induces apoptosis and induces autophagy. PI-1840 induces the accumulation of proteasome substrates p27, Bax, and IκB-α.
    PI-1840
  • HY-122808
    (-)-Camphoric acid
    Inducer 99.91%
    (-)-Camphoric acid is the less active enantiomer of Camphoric acid. Camphoric acid induces glutamate receptor expression. Camphoric acid also significantly induces the activation of NF-κB and AP-1. Camphoric acid significantly stimulates the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells. Camphoric acid has weak regulatory function towards glutamate receptors. Camphoric acid can induce mRNA expression of glutamate signaling molecules and activate transcription factors, thereby stimulating osteoblast differentiation.
    (-)-Camphoric acid
  • HY-P990018
    Boserolimab
    Activator 99.00%
    Boserolimab (MK-5890) is a humanized agonist monoclonal antibody that binds to CD27 to provide a costimulatory signal that enhances T-cell–mediated responses.
    Boserolimab
  • HY-N4327
    Eurycomalactone
    Inhibitor 99.74%
    Eurycomalactone is an active quassinoid could be isolated from Eurycoma longifolia Jack. Eurycomalactone is a potent NF-κB inhibitor with an IC50 value of 0.5 μM. Eurycomalactone inhibits protein synthesis and depletes cyclin D1. Eurycomalactone enhances radiosensitivity through arrest cell cycle at G2/M phase and delayed DNA double-strand break repair. Eurycomalactone inhibits the activation of AKT/NF-κB signaling, induces apoptosis and enhances chemosensitivity to Cisplatin (HY-17394).
    Eurycomalactone
  • HY-121955
    FW1256
    Inhibitor
    FW1256 is a phenyl analogue and a slow-releasing hydrogen sulfide (H2S) donor. FW1256 inhibits NF-κB activity and induces cell apoptosis. FW1256 exerts potent anti-inflammatory effects and has the potential for cancer and cardiovascular disease treatment.
    FW1256
  • HY-N2439
    Methyl isoeugenol
    Inhibitor 98.11%
    Methyl isoeugenol is an orally active, blood-brain barrier-permeable isoeugenol-type eugenol analog. Methyl isoeugenol promotes the nuclear translocation of Nrf2, upregulates the expressions of HO-1, NQO1 and SOD, and reduces the expression level of MDA. Methyl isoeugenol decreases the nuclear translocation of NF-κB. Methyl isoeugenol inhibits NLRP3 inflammasome-mediated pyroptosis. Methyl isoeugenol reduces cerebral infarction volume and regulates the M1/M2 phenotypic balance of microglia. Methyl isoeugenol can be used for the research of cerebral ischemia-reperfusion injury.
    Methyl isoeugenol
  • HY-N4231
    Lucyoside B
    Inhibitor 99.21%
    Lucyoside B inhibits the production of inflammatory mediators via both NF-κB and activator protein-1 pathways in activated macrophages.
    Lucyoside B
  • HY-B0516
    Articaine hydrochloride
    Inhibitor 99.38%
    Articaine (Hoe-045) hydrochloride is a selective inhibitor of voltage-gated sodium channels (such as rNav1.4, hNav1.7, and rNav1.8), with an IC50 of 15.8 μM for open-state Na+ channels, and IC50 of 40.6 μM and 378 μM for inactivated and resting-state Na+ channels, respectively. Articaine hydrochloride exerts local anesthetic activity by inhibiting Na+ influx to block nerve impulse conduction, and can also inhibit NF-κB activation and NLRP3 inflammasome pathways, exhibiting anti-inflammatory function. Articaine hydrochloride can be used in the study of dental local anesthesia and inflammatory-related diseases (such as acute kidney injury).
    Articaine hydrochloride
  • HY-N4314
    Scutellarein tetramethyl ether
    Inhibitor 99.93%
    Scutellarein tetramethyl ether (4',5,6,7-Tetramethoxyflavone) is a bioactive compound extracted from Eupatorium odoratum. Scutellarein tetramethyl ether exhibits anti-inflammatory, antibacterial, pro-coagulant, and anti-tumor activities. Scutellarein tetramethyl ether exerts its anti-inflammatory effects by modulating the NF-κB pathway and regulates bacterial resistance through the inhibition of efflux pumps. Additionally, Scutellarein tetramethyl ether accelerates coagulation time via the endogenous coagulation pathway. Studies have shown that Scutellarein tetramethyl ether can effectively inhibit the growth of the liver cancer cell line HepG2 (IC50= 20.08 μg/mL).
    Scutellarein tetramethyl ether
  • HY-N0143A
    Phlorizin dihydrate
    Inhibitor 99.51%
    Phlorizin (Floridzin) dihydrate is an orally active non-selective sodium-glucose cotransporter (SGLT) inhibitor, with an IC50 of 0.04 μM and a Ki of 39 nM against hSGLT2, and an IC50 of 0.17 μM and a Ki of 0.31 μM against hSGLT1. Phlorizin dihydrate promotes GLUT4 translocation, inhibits gluconeogenesis and promotes glycogen synthesis by activating the PI3K/Akt/mTOR pathway. Phlorizin dihydrate reduces DNA damage and apoptosis (apoptosis) by inhibiting the NF-κB inflammatory pathway. Phlorizin dihydrate induces apoptosis via activating the Caspase pathway by antagonizing the JAK/STAT3 and PCK pathways. Phlorizin dihydrate also exhibits antibacterial, anti-inflammatory and neuroprotective activities.
    Phlorizin dihydrate
  • HY-B1026
    Adelmidrol
    Inhibitor 98.0%
    Adelmidrol exerts important anti-inflammatory effects that are partly dependent on PPARγ. Adelmidrol reduces NF-κB translocation, and COX-2 expression.
    Adelmidrol
  • HY-P10030
    DPLG3
    Inhibitor 99.18%
    DPLG3 is a specific chymotryptic-like β5i subunits inhibitor, with an IC50 of 4.5 nM. DPLG3 inhibits mouse i-20S with IC50 of 9.4 nM. DPLG3 downregulates the protein levels of NF-κB p50 and p65. DPLG3 can be used for immune disease research.
    DPLG3
  • HY-N0390S3
    L-Glutamine-13C5,15N2,d5
    Inhibitor 99.91%
    L-Glutamine-13C5,15N2,d5 is the deuterium, 13C-, and 15N-labeled L-Glutamine (HY-N0390). L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na+-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.
    L-Glutamine-<sup>13</sup>C<sub>5</sub>,<sup>15</sup>N<sub>2</sub>,d<sub>5</sub>
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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