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-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-14928A
    Lobeglitazone sulfate
    		Inhibitor 99.63%
    Lobeglitazone sulfate is a new type of thiazolidinedione. Lobeglitazone sulfate is the orally active agonist for PPAR with EC50 of 137.4 nM and 546.3 nM for PPARγ and PPARα. Lobeglitazone sulfate is the inhibitor for ERK/JNK/Smad/NF-κB signaling pathway. Lobeglitazone sulfate exhibits anti-inflammatory, anti-diabetic, anti-fibrotic and anti-atherosclerotic properties.
    Lobeglitazone sulfate
  • 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-15027S1
    5-Aminosalicylic acid-d3
    		99.38%
    5-Aminosalicylic acid-d3 is the 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-d<sub>3</sub>
  • HY-P5275
    Tripeptide-41
    		Inducer 99.63%
    Tripeptide-41(CG-Lipoxyn)isa bioactive peptide withreduce fat accumulationeffect and has been reported used as a cosmetic ingredient.
    Tripeptide-41
  • HY-112433A
    (S)-NIK SMI1
    		Control 99.28%
    (S)-NIK SMI1 is the isomer of NIK SMI1 (HY-112433), and can be used as an experimental control. NIK SMI1 is a potent, selective NF-κB inducing kinase (NIK) inhibitor, which inhibits NIK-catalyzed hydrolysis of ATP to ADP with IC50 of 0.23±0.17 nM.
    (S)-NIK SMI1
  • HY-112433A
    (S)-NIK SMI1
    		Inhibitor 99.28%
    (S)-NIK SMI1 is the isomer of NIK SMI1 (HY-112433), and can be used as an experimental control. NIK SMI1 is a potent, selective NF-κB inducing kinase (NIK) inhibitor, which inhibits NIK-catalyzed hydrolysis of ATP to ADP with IC50 of 0.23±0.17 nM.
    (S)-NIK SMI1
  • HY-N2157
    Pteryxin
    		Inhibitor 99.96%
    Pteryxin ((+)-Pteryxin) is an orally active multi-target inhibitor that targets NF-κB, MAPK, NLRP3 inflammasome, and Nrf2/ARE pathways. Pteryxin is also a BChE inhibitor (IC50=12.96 μg/mL) with a low inhibitory efficiency on AChE. Pteryxin inhibits the Ca2+-calcineurin-NFATc1 pathway by blocking NF-κB/MAPK signaling, inhibiting NLRP3 inflammasome activation, and reducing ROS generation, and activates Nrf2-mediated antioxidant enzyme expression. Pteryxin has anti-inflammatory, antioxidant, and osteoclastogenesis inhibitory activities. Pteryxin can be used in the study of inflammatory diseases, osteoporosis, diabetes, and Alzheimer's disease.
    Pteryxin
  • HY-N2205
    Esculentoside H
    		Inhibitor 98.73%
    Esculentoside H (EsH) is a saponin isolated from the root extract of perennial plant Phytolacca esculenta. Esculentoside H (EH) has anti-tumor activity, the mechanism is related to the capacity for TNFrelease. Esculentoside H (EsH) suppresses colon cancer cell migration through blockage of the JNK1/2 and NF-κB signaling-mediated matrix metalloproteinases-9 (MMP-9) expression.
    Esculentoside H
  • HY-N0385
    Gomisin J
    		Inhibitor 99.88%
    Gomisin J is a Schisandra chinensis-derived lignan that can inhibit multiple targets such as eNOS, AMPK (LKB1, CaMKIIβ), fetuin-A, NF-κB, Nrf2/HO-1, and can pass through the blood-brain barrier. Gomisin J increases NO bioavailability by activating eNOS, regulates lipid metabolism by activating the AMPK pathway, inhibits fetuin-A and NF-κB to exert anti-inflammatory effects, and activates Nrf2/HO-1 to enhance antioxidant capacity. Gomisin J has the activities of anti-hypertension, regulating liver lipid metabolism, and reducing cerebral ischemia-reperfusion injury, and can be used for research on hypertension, non-alcoholic fatty liver disease, cerebral ischemia-reperfusion injury, etc.
    Gomisin J
  • HY-W011849
    Phenyl β-D-glucopyranoside
    		Inhibitor 99.85%
    Phenyl β-D-glucopyranoside has anti-cancer and anti-inflammatory activities. Phenyl β-D-glucopyranoside inhibits nitric oxide (NO) production, and the expression of iNOS and COX-2. Phenyl β-D-glucopyranoside also inhibits the nuclear translocation of NF-κB.
    Phenyl β-D-glucopyranoside
  • HY-N6826
    Asatone
    		Activator 99.94%
    Asatone is an active component isolated from Radix et Rhizoma Asari, with anti-inflammatory effect via activation of NF-κB and donwn regulation of p-MAPK (ERK, JNK and p38) pathways.
    Asatone
  • HY-N0197R
    Baicalin (Standard)
    		Inhibitor
    Baicalin (Standard) is the analytical standard of Baicalin. This product is intended for research and analytical applications. Baicalin, as a flavonoid glycoside, is an allosteric carnitine palmityl transferase 1 (CPT1) activator. Baicalin reduces the expression of NF-κB.
    Baicalin (Standard)
  • HY-157793
    SMU-L11
    		Activator 99.64%
    SMU-L11 is a specific TLR7 agonist (EC50=0.024 μM), which recruits MyD88 adapter protein and activates downstream NF-κB and MAPK signaling pathways. In murine models, SMU-L11 significantly enhances immune cell activation and promotes the proliferation of CD4+ T and CD8+ T cells, thereby directly killing tumor cells and inhibiting tumor growth. SMU-L11 can be used for cancer research, and also has the potential for studying immune system diseases.
    SMU-L11
  • HY-W001925
    7-Methoxy-1-tetralone
    		Inhibitor 99.93%
    7-Methoxy-1-tetralone is a potent antitumor agent. 7-Methoxy-1-tetralone inhibits cancer cell proliferation and migration, and induces hepatocellular carcinoma cell (HCC) apoptosis. 7-Methoxy-1-tetralone decreased the protein levels of NF-κB, matrix metallopeptidase 2 (MMP2)/MMP9, and p-AKT. 7-Methoxy-1-tetralone showed antitumor activity in nude mice and had no effect on body weight and liver, spleen and organ index.
    7-Methoxy-1-tetralone
  • HY-N1731
    2′-Hydroxy-5′-methoxyacetophenone
    		Inhibitor 99.96%
    2'-Hydroxy-5'-methoxyacetophenone is an acetophenone derivative with acaricidal activities. 2'-Hydroxy-5'-methoxyacetophenone attenuates the inflammatory response via NF-κB signaling pathway. 2'-Hydroxy-5'-methoxyacetophenone exhibits significant inhibitory activity against α-amylase, collagenase and aldose reductase (AR) with IC50s of 0.928, 3.264 and 20.046 μM, highlighting its potential in combating diabetes. 2'-Hydroxy-5'-methoxyacetophenone exhibits anti-ovarian cancer activity.
    2′-Hydroxy-5′-methoxyacetophenone
  • HY-N0290R
    Mangiferin (Standard)
    		Inhibitor
    Mangiferin (Standard) is the analytical standard of Mangiferin. This product is intended for research and analytical applications. Mangiferin is a Nrf2 activator. Mangiferin suppresses nuclear translocation of the NF-κB subunits p65 and p50. Mangiferin exhibits antioxidant, antidiabetic, antihyperuricemic, antiviral, anticancer and antiinflammatory activities.
    Mangiferin (Standard)
  • HY-N2303
    Eriocalyxin B
    		Inhibitor 99.93%
    Eriocalyxin B is a diterpenoid compound that can be isolated from Chinese herb Isodon eriocalyx. Eriocalyxin B exhibits multiple activities, such as anti-cancer, anti-inflammatory, and inhibition of adipogenesis. Eriocalyxin B is capable of inducing apoptosis and autophagy in tumor cells. Eriocalyxin B can be used in the research of cancers, autoimmune diseases, and other conditions.
    Eriocalyxin B
  • HY-N1993
    5-Methyl-7-methoxyisoflavone
    		Inhibitor 99.78%
    5-Methyl-7-methoxyisoflavone is an orally active anti-oxidant with remyelinating activity. 5-Methyl-7-methoxyisoflavone inhibits the enzyme aromatase, interfering with the normal metabolic pathways of testosterone. 5-Methyl-7-methoxyisoflavone is a non-steroidal anabolic isoflavone, used as a anabolic agent. 5-Methyl-7-methoxyisoflavone shows better potency increasing muscle mass and endurance than Ipriflavone (HY-N0094). 5-Methyl-7-methoxyisoflavone can be used for fat loss besides the maintenance of low cholesterol level and strengthen bones. 5-Methyl-7-methoxyisoflavone is the inhibitor for NF-κB.
    5-Methyl-7-methoxyisoflavone
  • HY-N9942
    Physalin A
    		Inhibitor 99.22%
    Physalin A is a biologically active withanolide. Physalin A shows anti-inflammatory, antifibrotic and ameliorative effects on autophagy in models of disc degeneration. Physalin A has antitumor activity and can induce apoptosis, ROS production and G2/M phase cell cycle arrest. Besides. Physalin A can significantly increase the activity of quinone reductase and increase the expression of detoxifying enzymesc.
    Physalin 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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