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-B0380S2
    Trimebutine-d3 hydrochloride
    		Inhibitor
    Trimebutine-d3 hydrochloride is deuterium labeled Trimebutine hydrochloride. Trimebutine hydrochloride is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine hydrochloride inhibits L-type Ca2+ channels and large-conductance calcium-activated potassium channels (BKCa channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine hydrochloride also targets Toll-like receptors, inhibits Toll-like receptor 2/4/7/8/9 signals, and inhibits LPS-induced IRAK1 activation, as well as ERK1/2, JNK and NF-κB activation, thereby exerting anti-inflammatory effects. Trimebutine hydrochloride also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine hydrochloride also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS).
    Trimebutine-d<sub>3</sub> hydrochloride
  • HY-175222
    GlcNAc-MurNAc
    		Inhibitor
    GlcNAc-MurNAc, a disaccharide, is a TLR4 agonist with a Kd of 383 μM for murine TLR4. GlcNAc-MurNAc directly binds to TLR4 and activates its downstream NF-κB and IRF pathways. GlcNAc-MurNAc improves Dextran sulfate sodium salt (DSS) (HY-116282C)-induced colitis in mice through a TLR4-dependent mechanism. GlcNAc-MurNAc can be used for the study of inflammatory bowel disease.
    GlcNAc-MurNAc
  • HY-155753
    Anti-inflammatory agent 50
    		Inhibitor
    Anti-inflammatory agent 50 (compound a1) is a Fusidic acid derivative with anti-inflammatory effects. Anti-inflammatory agent 50 inhibits inflammatory factor NO, IL-6 and TNF-α. Anti-inflammatory agent 50 alleviates acute lung injury by regulating inflammatory mediators and suppressing the MAPK, NF-κB and NLRP3 inflammasome signaling pathways.
    Anti-inflammatory agent 50
  • HY-N6949R
    Juglone (Standard)
    		Inhibitor
    Juglone (Standard) is the analytical standard of Juglone. This product is intended for research and analytical applications. 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 (Standard)
  • HY-P991598
    MOR-106
    		Inhibitor
    MOR-106 (MOR12743) is a humanized anti-IL-17C IgG1 monoclonal antibody. MOR-106 inhibits the NF-κB signaling pathway by specifically binding to IL-17C (IC50 = 59 pM for human IL-17C, IC50 = 55 pM for mouse IL-17C). MOR-106 can effectively inhibit skin inflammation and reduce related inflammatory factors in animal models of psoriasis and atopic dermatitis.
    MOR-106
  • HY-148475
    (R)-SEMBL
    		Inhibitor
    (R)-SEMBL (compound 1B) is a potent NF-κB inhibitor. (R)-SEMBL can be used for the research of cancer, inflammation, autoimmune diseases, diabetes and diabetes complications, infections, cardiovascular disease and defective reperfusion injury.
    (R)-SEMBL
  • HY-N0106R
    (Rac)-Salvianic acid A sodium (Standard)
    		Inhibitor
    (Rac)-Salvianic acid A (sodium) (Standard) is the analytical standard of (Rac)-Salvianic acid A (sodium). This product is intended for research and analytical applications. (Rac)-Salvianic acid A sodium is the racemic form of Salvianic acid A (HY-N1913). Salvianic acid A is an orally active phenolic compound that induces Nrf2/HO-1 activation and inhibits the NF-κB pathway, and it also activates the mitochondrial antioxidant defense system (Mitochondrial Metabolism). Salvianic acid A exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties (Apoptosis), demonstrating potential for research into inflammation and cardiovascular diseases.
    (Rac)-Salvianic acid A sodium (Standard)
  • HY-B0185BR
    Lidocaine hydrochloride hydrate (Standard)
    		Inhibitor
    Lidocaine (hydrochloride hydrate) (Standard) is the analytical standard of Lidocaine (hydrochloride hydrate). This product is intended for research and analytical applications. Lidocaine (Lignocaine) hydrochloride hydrate inhibits sodium channels involving complex voltage and using dependence. Lidocaine hydrochloride hydrate 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 hydrate is an amide derivative and has potential for the research of ventricular arrhythmia.
    Lidocaine hydrochloride hydrate (Standard)
  • HY-134000
    Emodic acid
    		Inhibitor
    Emodic acid (NSC624610) is an anthraquinone compound isolated from A. microcarpus, which can inhibit the proliferation of cancer cells by inhibiting the activity of NF-κB. Emodic acid can also inhibit the phosphorylation of p38, ERK and JNK, the secretion of tumor-promoting cytokines IL-1β and IL-6, and the expression of VEGF and MMP, thereby inhibiting the invasion and migration potential of cancer cells.
    Emodic acid
  • HY-123461
    Sul-121 hydrochloride
    		Inhibitor
    Sul-121 hydrochloride is a novel compound with anti-oxidative capacity that effectively inhibits airway inflammation and hyperresponsiveness (AHR) in experimental models of chronic obstructive pulmonary disease (COPD). Sul-121 hydrochloride prevents lipopolysaccharide-induced airway neutrophilia and AHR in a dose-dependent manner. Sul-121 hydrochloride also demonstrates the ability to reduce oxidative stress markers in human airway smooth muscle cells. Sul-121 hydrochloride inhibits nuclear translocation of the NF-κB subunit, p65, thereby diminishing pro-inflammatory cytokine release.
    Sul-121 hydrochloride
  • HY-N10009
    Cudraflavone B
    		Modulator
    Cudraflavone B is a prenylated flavonoid with anti-inflammatory and anti-tumor properties. Cudraflavone B is also a dual inhibitor of COX-1 and COX-2. Cudraflavone B blocks the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages. Thus, Cudraflavone B inhibits tumor necrosis factor α (TNFα) gene expression and secretion. Cudraflavone B also triggers the mitochondrial apoptotic pathway, activates NF-κB, the MAPK p38, and ERK, and induced the expression of SIRT1. Thus Cudraflavone B inhibits the growth of human oral squamous cell carcinoma cells.
    Cudraflavone B
  • HY-139833
    Anti-inflammatory agent 6
    Anti-inflammatory agent 6 blocks the phosphorylation of I kappa b kinase α/β (IKKα/β), IκBα, and nuclear factor kB p65 (NF-κB p65) which is a key controller of inflammation, thereby showing anti-inflammatory potential.
    Anti-inflammatory agent 6
  • HY-170218
    NLRP3-IN-76
    		Inhibitor
    NLRP3-IN-76 is an orally active NLRP3 inhibitor. NLRP3-IN-76 inhibits the production of NO, and the mRNA levels of proinflammatory cytokines (iNOS, IL-6, IL-1β and TNFα). NLRP3-IN-76 shows anti-inflammatory effects by inhibiting the activation of the NLRP3 inflammasome and NF-κB signaling pathway. NLRP3-IN-76 ameliorates DSS (HY-116282C)-induced colitis and can be used for research of inflammatory bowel diseases (IBD).
    NLRP3-IN-76
  • HY-176251
    CBP/p300-IN-22
    		Inhibitor
    CBP/p300-IN-22 is a selective CBP/EP300-BRD inhibitor with an IC50 of 4 nM. CBP/p300-IN-22 is highly selective over BRD4(1). CBP/p300-IN-22 reduces TNF-α-induced cytokine expression and subsequent immune cell recruitment by inhibiting NF-κB signaling, and has anticancer activity. CBP/p300-IN-22 can be used for the research of rheumatoid arthritis (RA) and other TNF-α-mediated inflammatory conditions.
    CBP/p300-IN-22
  • HY-N3602A
    rel-Cleroindicin F
    		Inhibitor
    rel-Cleroindicin F (Rengyolone) is a cyclohexyl acetyl compound that can be isolated from the fruit of forsythia and has anti-inflammatory activity. It strongly inhibits the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). rel-Cleroindicin F does this by downregulating the activity of NF-κB and NF-κB kinases in RAW 264.7 cells stimulated by LPS (HY-D1056), thus inhibiting the expression of inducible nitric oxide synthase (NO Synthase) and nitric oxide production.
    rel-Cleroindicin F
  • HY-176192
    SMU-14a
    		Inhibitor
    SMU-14a is a TLR3 inhibitor (IC50: 0.18 µM). SMU-14a inhibits IL-6 secretion in mouse peritoneal macrophages and downregulates TNF-α in human peripheral blood monocytes. SMU-14a exerts anti-inflammatory effects by reducing the phosphorylation of p65, ERK, and TBK1 through NF-κB, MAPK, and IRF3 signaling pathways, and decreasing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. SMU-14a can be used in the study of acute hepatitis.
    SMU-14a
  • HY-139844
    Anti-inflammatory agent 7
    		Inhibitor
    Anti-inflammatory agent 7 inhibits proinflammatory cytokines by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells as well as mice.
    Anti-inflammatory agent 7
  • HY-N0387R
    Rhynchophylline (Standard)
    		Inhibitor
    Rhynchophylline (Standard) is the analytical standard of Rhynchophylline. This product is intended for research and analytical applications. 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 (Standard)
  • HY-N1500S1
    Pulegone-d8
    		Inhibitor
    Pulegone-d8 is deuterated labeled Pulegone (HY-N1500). Pulegone is a monoterpene ketone compound widely present in the essential oils of many plants. Pulegone can also be used as a bird repellent. Pulegone has multiple activities such as anti-inflammatory, antibacterial, antifungal, and anti-hyperalgesic effects. Pulegone is particularly effective against bacteria of the Salmonella species.
    Pulegone-d<sub>8</sub>
  • HY-N2117R
    Isoginkgetin (Standard)
    		Inhibitor
    Isoginkgetin (Standard) is the analytical standard of Isoginkgetin. This product is intended for research and analytical applications. Isoginkgetin is a pre-mRNA splicing inhibitor inhibitor. Isoginkgetin also inhibits activities of both Akt, NF-κB and MMP-9. Isoginkgetin inhibits the activity of the 20S proteasome, induces apoptosis and activates autophagy.
    Isoginkgetin (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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