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-124445
    APC0576
    Inhibitor
    APC0576 is an inhibitor for the activation of NF-κB signaling pathway, and inhibits the activation of NF-κB depedent gene (IC50 is 1.0 μM for β-gal). APC0576 inhibits IL-1-induced chemokines release, and can be used in research about pathological endothelial cell activation releted diseases.
    APC0576
  • HY-D0205AS1
    Carbocisteine-13C3-1
    Inhibitor
    Carbocisteine-13C3-1 (Carbocysteine-13C3-1) is 13C labeled Carbocisteine. 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-<sup>13</sup>C3-1
  • HY-15027S4
    5-Aminosalicylic acid-d7
    Inhibitor
    5-Aminosalicylic acid-d7 (5-ASA-d7; Mesalamie-d7; Mesalazie-d7) is deuterium labeled 5-Aminosalicylic Acid. 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-d<sub>7</sub>
  • HY-N0806R
    Sweroside (Standard)
    Inhibitor
    Sweroside (Standard) is the analytical standard of Sweroside (HY-N0806). This product is intended for research and analytical applications. Sweroside is an iridoid glycoside that targets multiple targets, including the Keap1/Nrf2 axis, NLRP3 inflammasome, SIRT1, NF-κB, AMPK/mTOR pathway, and caspase family. Sweroside promotes Nrf2 nuclear translocation by competitively binding to Keap1. Sweroside also inhibits oxidative stress and NLRP3-mediated pyroptosis by activating Nrf2, inhibits NF-κB inflammatory pathway by activating SIRT1, and promotes autophagy and induces caspase-dependent apoptosis via the AMPK/mTOR pathway. Sweroside has antioxidant, anti-inflammatory, anti-apoptotic, and lipid metabolism regulating activities, and can be used in the research of myocardial ischemia-reperfusion injury, leukemia, acute lung injury, non-alcoholic fatty liver disease, and other fields.
    Sweroside (Standard)
  • HY-10071R
    Y-27632 (Standard)
    Inhibitor
    Y-27632 (Standard) is the analytical standard of Y-27632 (HY-10071). This product is intended for research and analytical applications. Y-27632 is a ROCK inhibitor with Ki values of 220 nM and 300 nM for ROCK1 and ROCK2, respectively. Y-27632 exerts anti-inflammatory and immunomodulatory effects in systemic lupus erythematosus models by inhibiting the ROCK/NF-κB pathway. Y-27632 enhances autophagy by inhibiting the AKT/mTOR pathway, thereby inducing apoptosis apoptosis in oral squamous cell carcinoma. Y-27632 induces the formation of tunneling nanotubes in ARPE-19 cells and significantly enhances mitochondrial transfer through these channels. Y-27632 promotes neurite outgrowth in PC12 cells by activating the Rac1/NOX1/ROS/AKT/PAK1 signaling cascade.
    Y-27632 (Standard)
  • HY-B0167AR
    Sodium Salicylate (Standard)
    Inhibitor
    Sodium Salicylate (Standard) is the analytical standard of Sodium Salicylate. This product is intended for research and analytical applications. Sodium Salicylate (Salicylic acid sodium salt) inhibits cyclo-oxygenase-2 (COX-2) activity independently of transcription factor (NF-κB) activation. Sodium Salicylate is also a S6K inhibitor.Sodium Salicylate is a NF-κB inhibitor that decreases inflammatory gene expression and improves repair in aged muscle.
    Sodium Salicylate (Standard)
  • HY-10072R
    SPC 839 (Standard)
    Inhibitor
    SPC 839 (Standard) is the analytical standard of SPC 839 (HY-10072). This product is intended for research and analytical applications. SPC 839 (compound 10) is an orally active inhibitor of AP-1 and NF-kB mediated transcriptional activation with IC50 of 0.008 μM.
    SPC 839 (Standard)
  • HY-123185
    (Rac)-Z-FA-FMK
    Inhibitor
    (Rac)-Z-FA-FMK is the racemate of Z-FA-FMK. (Rac)-Z-FA-FMK is an inhibitor of cathepsin B with a Ki of 1.5 μM. (Rac)-Z-FA-FMK inhibits caspase-2, -3, -6, -7, and -9 with IC50s of 6.147, 15.41, 32.45, 9.077, and 110.7 μM. (Rac)-Z-FA-FMK inhibits the main protease of SARS-CoV-2 replication with an IC50 of 11.39 μM. (Rac)-Z-FA-FMK inhibits the increased IL-1β level induced by LPS and NF-κB transactivation in macrophages.
    (Rac)-Z-FA-FMK
  • HY-126307R
    Urolithin B (Standard)
    Inhibitor
    Urolithin B (Standard) is the analytical standard of Urolithin B. This product is intended for research and analytical applications. Urolithin B is one of Ellagitannins' slow microbial products, and has anti-inflammatory and anti-inflammatory effects. Urolithin B suppresses NF-κB activity. Urolithin B suppresses JNK, ERK and Akt's oxidation, and increases AMPK's oxidation. Urolithin B is also a quantitative change factor for bone and skin quality.
    Urolithin B (Standard)
  • HY-124284R
    Hexamethylene bisacetamide (Standard)
    Inhibitor
    Hexamethylene bisacetamide (Standard) is the analytical standard of Hexamethylene bisacetamide. This product is intended for research and analytical applications. Hexamethylene bisacetamide (HMBA) is a differentiation inducer and selective bromine domain inhibitor that can differentiate across the blood-brain barrier. Hexamethylene bisacetamide can induce tumor cell differentiation and inhibit cell proliferation, showing antitumor activity. Hexamethylene bisacetamide induces apoptosis by Notch1, Bcl-2 and p53 signaling pathways. In addition, Hexamethylene bisacetamide improves the obesity phenotype of mice.
    Hexamethylene bisacetamide (Standard)
  • HY-107632R
    GYY4137 (Standard)
    Inhibitor
    GYY4137 (Standard) is the analytical standard of GYY4137 (HY-107632). This product is intended for research and analytical applications. GY4137 is a sustained-release H2S donor possessing vasodilatory, antihypertensive, and anti-inflammatory activities. GY4137 can inhibit cell growth, induce apoptosis, and cause cell cycle arrest by blocKing the STAT3 pathway, demonstrating potent anticancer activity.
    GYY4137 (Standard)
  • HY-117429
    Se-Aspirin
    Inhibitor
    Se-Aspirin is a hybrid molecule of selenium and Aspirin (HY-14654). Se-Aspirin reduces the viability of cancer cell lines, particularly colorectal cancer cells.
    Se-Aspirin
  • HY-B1114R
    Gliquidone (Standard)
    Inhibitor
    Gliquidone (Standard) is the analytical standard of Gliquidone. This product is intended for research and analytical applications. Gliquidone can bind to the pancreatic β-cells and increases insulin release to regulate blood glucose levels. Gliquidone significantly decreases LPS (HY-D1056)-induced proinflammatory responses and inhibits ERK/STAT3/NF-κB phosphorylation in BV2 microglial cells. Gliquidone can suppress microgliosis, microglial hypertrophy mediated by LPS, and proinflammatory cytokine COX-2 and IL-6 levels in murine model. Gliquidone also exhibits good anticancer activity in lung carcinoma cells. Gliquidone has antioxidant property. Gliquidone can be studied in research for type 2 diabetes and cancers.
    Gliquidone (Standard)
  • HY-N0510R
    Aristolochic acid A (Standard)
    Inhibitor
    Aristolochic acid A (Standard) is the analytical standard of Aristolochic acid A. This product is intended for research and analytical applications. Aristolochic acid A (Aristolochic acid I; TR 1736) is the main component of plant extract Aristolochic acids, which are found in various herbal plants of genus Aristolochia and Asarum. Aristolochic acid A significantly reduces both activator protein 1 (AP-1) and NF-κB activities. Aristolochic acid A reduces BLCAP gene expression in human cell lines.
    Aristolochic acid A (Standard)
  • HY-18620R
    DZ2002 (Standard)
    Inhibitor
    DZ2002 (Standard) is the analytical standard of DZ2002. This product is intended for research and analytical applications. DZ2002 is an orally active, reversible and low-cytotoxic type III SAHH inhibitor (Ki=17.9 nM), with good immunosuppressive activity. DZ2002 prevents the development of experimental dermal fibrosis by reversing the profibrotic phenotype of various cell types. DZ2002 can be used in studies of autoimmune diseases such as lupus syndrome and systemic sclerosis.
    DZ2002 (Standard)
  • HY-N0298R
    Stachydrine (Standard)
    Inhibitor
    Stachydrine (Standard) is the analytical standard of Stachydrine. This product is intended for research and analytical applications. 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 (Standard)
  • HY-118312
    CAY10657
    Inhibitor
    CAY10657 is an inhibitor for NF-κB pathway. CAY10657 downregulates expressions of proinflammatory cytokine (IL-6) and chemokine (MCP-1), and thus exhibits anti-inflammatory efficacy against meningitis induced by Streptococcus suis.
    CAY10657
  • HY-B1014S
    Acenocoumarol-d5
    Inhibitor
    Acenocoumarol-d5 is the deuterium labeled Acenocoumarol (HY-B1014). Acenocoumarol is an anticoagulant that functions as a Vitamin K antagonist. Acenocoumarol inhibits MAPK/ERK/JNK signaling pathway, reduces the nuclear translocation of NF-κB p65, activates Akt/GSK3β signaling pathway. Acenocoumarol induces apoptosis in cell A549, arrests cell cycle at S phase.
    Acenocoumarol-d<sub>5</sub>
  • HY-N16435
    Plumericin
    Inhibitor
    Plumericin is an anti-inflammatory, antioxidant, and antibacterial agent. Plumericin reduces Apoptosis, promotes Nrf-2 and inhibits NF-κB and AhR activation, blocks STAT3 signaling. Plumericin inhibits Mycobacterium tuberculosis growth. Plumericin can be used for the research of chronic kidney disease, vascular diseases, inflammatory bowel diseases, peritonitis, and tuberculosis.
    Plumericin
  • HY-N0481R
    Roburic acid (Standard)
    Inhibitor
    Roburic acid (Standard) is the analytical standard of Roburic acid. This product is intended for research and analytical applications. Roburic acid acts as an anti-inflammatory, anti-tumor and osteoclastogenesis inhibitor, with a Ki of 7.066 μM against human TNF, an IC50 of 9 μM against human COX-2, and an IC50 of 5 μM against ovine COX-1. Roburic acid reduces the production of inflammatory mediators such as NO and IL-6 in macrophages by inhibiting the NF-κB and MAPK (p38/JNK) pathways. By competitively inhibiting the TNF-TNF-R1 interaction, Roburic acid blocks the downstream NF-κB signaling pathway, thereby inducing cell cycle arrest and apoptosis in cancer cells. Roburic acid specifically inhibits osteoclastogenesis and bone resorption by suppressing the RANKL/TRAF6/NF-κB/NFATc1 axis. Roburic acid can be used in research related to osteolytic diseases such as osteoporosis, colorectal cancer and inflammatory diseases.
    Roburic acid (Standard)
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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