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-139715
    IMD-ferulic
    		Modulator
    IMD-ferulic is a covalently linked NF-κB modulator that improves the adjuvanticity of small molecule immune potentiators.
    IMD-ferulic
  • HY-P11093
    Papiliocin
    		Inhibitor
    Papiliocin is a potent peptide antibiotic with both anti-inflammatory and antibacterial activities. Papiliocin is primarily active against Gram-negative bacteria. Papiliocin exhibits strong anti-inflammatory activity against cell, exerting its anti-inflammatory activity by inhibiting the production of NO and the secretion of TNF-α and MIP-2. Papiliocin participates in the innate defense response mechanism by inhibiting the Toll-like receptor pathway and NF-κB. Papiliocin induces apoptosis in fungal cells and increases the total level of intracellular ROS. Papiliocin acts as an effective antiseptic peptide in sepsis models. Papiliocin is useful in anti-inflammatory and antibacterial research.
    Papiliocin
  • HY-143243
    Antioxidant agent-5
    		Inhibitor
    Antioxidant agent-5 (compound D-6) is a potent antioxidant agent. Antioxidant agent-5 can inhibit oxLDL (oxidized low-density lipoprotein)-induced apoptosis and the expression of ICAM-1 and VCAM-1 in VECs. Antioxidant agent-5 suppresses oxLDL-induced increase of ROS level and nuclear translocation of NF-κB. Antioxidant agent-5 protects against oxLDL-induced endothelial injury by activating Nrf2/HO-1 anti-oxidation pathway.
    Antioxidant agent-5
  • HY-P2670
    SN50M
    		Control
    SN50M, a mutant peptide of SN50 (HY-P0151), is a cell membrane-permeable inactive control peptide.
    SN50M
  • HY-175007
    RIPK1-IN-32
    		Inhibitor
    RIPK1-IN-32 is a RIPK inhibitor with anti-inflammatory activity. RIPK1-IN-32 inhibits nitric oxide (NO) release with an IC50 of 3.26 μM. RIPK1-IN-32 significantly alleviates acute liver injury associated with sepsis through the RIPK1/NF-κB/MAPK pathway, therefore preventing the nuclear translocation of p65 and c-fos, which results in reduced expression of TNF-α and IL-6. RIPK1-IN-32 can be used for the study of acute liver injury and sepsis.
    RIPK1-IN-32
  • HY-N7182
    9,10-Dimethoxycanthin-6-one
    		Inhibitor
    9,10-Dimethoxycanthin-6-one is an alkaloid compound. 9,10-Dimethoxycanthin-6-one exhibits NF-κB inhibitory effects with an IC50 of 19.5 μM.
    9,10-Dimethoxycanthin-6-one
  • HY-147836
    Akt/NF-κB/JNK-IN-1
    		Inhibitor
    Akt/NF-κB/JNK-IN-1 (Compound 2i) is an inhibitor of Akt, NF-κB and JNK signaling pathways. Akt/NF-κB/JNK-IN-1 inhibits nitric oxide production with an IC50 of 3.15 μM. Akt/NF-κB/JNK-IN-1 shows anti-inflammatory activities.
    Akt/NF-κB/JNK-IN-1
  • HY-N0622R
    Morusin (Standard)
    		Inhibitor
    Morusin (Standard) is the analytical standard of Morusin. This product is intended for research and analytical applications. Morusin is a prenylated flavonoid isolated from Morus alba Linn. with various biological activities, such as antitumor, antioxidant, and anti-bacteria property. Morusin could inhibit NF-κB and STAT3 activity.
    Morusin (Standard)
  • HY-W744739
    Betulinic acid-d3
    Betulinic acid-d3 (Lupatic acid-d3) is a deuterium labeled Betulinic acid (HY-10529). Betulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties.
    Betulinic acid-d<sub>3</sub>
  • HY-N0031R
    Plantamajoside (Standard)
    		Inhibitor
    Plantamajoside (Standard) is the analytical standard of Plantamajoside. This product is intended for use in research and analytical applications. Plantamajoside is an orally active phenylpropanoid glycoside. Plantamajoside can be isolated from Plantago asiatica L.(Plantaginaceae). Plantamajoside inactivates NF-κB, PI3K/akt, induces Apoptosis, and improves Autophagy. Plantamajoside regulates MAPK, integrin-linked kinase/c-Src. Plantamajoside inhibits multiple cancers, improves lung and kidney damage. Plantamajoside has neuroprotective and anti-inflammatory effects.
    Plantamajoside (Standard)
  • HY-W015490R
    1,4-Naphthoquinone (Standard)
    		Inhibitor
    1,4-Naphthoquinone is an inhibitor with broad-spectrum inhibitory activity targeting DNA polymerase, NF-κB and monoamine oxidase (MAO-A/B), with antibacterial and anti-biofilm efficacy. 1,4-Naphthoquinone is a competitive inhibitor of MAO-B (Ki=1.4 μM) and a non-competitive inhibitor of MAO-A (Ki=7.7 μM). 1,4-Naphthoquinone inhibits DNA polymerase pol α, β, γ, δ, ε, λ with IC50 ranging from 5.57-128 μM. 1,4-Naphthoquinone inhibits tumor cell proliferation, induces apoptosis and necrosis, and has anti-angiogenic and anti-inflammatory activities by inducing oxidative stress, depleting glutathione (GSH), inhibiting DNA polymerase-mediated DNA synthesis and blocking NF-κB nuclear translocation. 1,4-Naphthoquinone can be used in anti-bacterial , anti-tumor and anti-inflammatory studies, including inhibition of melanoma and colon cancer cell growth and endothelial cell function, as well as LPS-induced inflammation models.
    1,4-Naphthoquinone (Standard)
  • HY-B0130R
    Perindopril (Standard)
    Perindopril (Standard) is the analytical standard of Perindopril. This product is intended for research and analytical applications. Perindopril (S-9490) is an orally available, long-acting angiotensin-converting enzyme (ACE) inhibitor. Perindopril inhibits inflammatory cell influx and intimal thickening, preserving elastin on the inside of the aorta. Perindopril effectively inhibits experimental abdominal aortic aneurysm (AAA) formation in a rat model and reduces pulmonary vasoconstriction in rats with pulmonary hypertension.
    Perindopril (Standard)
  • HY-N1965R
    Gaultherin (Standard)
    		Inhibitor
    Gaultherin (Standard) is the analytical standard for Gaultherin (HY-N1965). Gaultherin is an orally active non-steroidal anti-inflammatory agent. Gaultherin selectively inhibits NF-κB, MAPK, COX-2 (IC50 = 0.35 mg/mL), LOX (IC50 = 0.56 mg/mL) and HYAL (IC50 = 28.58 μg/mL) to exert anti-inflammatory, antipyretic and analgesic effects. Gaultherin exhibits modest direct antioxidant capacity, greater in cell-based models. Gaultherin does not affect COX-1 so that avoids the common gastrointestinal side effects of Aspirin (HY-14654).
    Gaultherin (Standard)
  • HY-135444
    Heliangin
    		Inhibitor
    Heliangin is a Sesquiterpenoids product that can be isolated from the herbs of Helianthus tuberosus L..
    Heliangin
  • HY-N0634R
    Cimifugin (Standard)
    		Inhibitor
    Cimifugin (Standard) is the analytical standard of Cimifugin. This product is intended for research and analytical applications. Cimifugin (Cimitin) is a bioactive component of Cimicifuga racemosa, a Chinese herb. Cimifugin suppresses allergic inflammation by reducing epithelial derived initiative key factors via regulating tight junctions. Cimifugin reduces the migration and chemotaxis of RAW264.7 cells and inhibits the release of inflammatory factors and activation of MAPKs and NF-κB signaling pathways induced by LPS.
    Cimifugin (Standard)
  • HY-N6966R
    Ethyl Caffeate (Standard)
    		Inhibitor
    Ethyl Caffeate is a natural phenolic compound isolated from Bidens pilosa. Ethyl caffeate suppresses NF-κB activation and its downstream inflammatory mediators, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in vitro or in mouse skin.
    Ethyl Caffeate (Standard)
  • HY-N0919R
    Yangonin (Standard)
    		Inhibitor
    Yangonin (Standard) is the analytical standard of Yangonin. This product is intended for research and analytical applications. Yangonin exhibits affinity for the human recombinant cannabinoid CB1 receptor with an IC50 and a Ki of 1.79 μM and 0.72 μM, respectively.
    Yangonin (Standard)
  • HY-N3021R
    D-chiro-Inositol (Standard)
    		Inhibitor
    D-chiro-Inositol is a stereoisomer of inositol that exhibits activities such as improving glucose metabolism, anti-tumor effects, anti-inflammatory properties, and antioxidant activity. D-chiro-Inositol effectively alleviates cholestasis by enhancing bile acid secretion and reducing oxidative stress. D-chiro-Inositol improves insulin resistance, lowers hyperglycemia and circulating insulin levels, reduces serum androgen levels, and ameliorates some metabolic abnormalities associated with X syndrome by mimicking the action of insulin. Additionally, D-chiro-Inositol can induce a reduction in pro-inflammatory factors (such as Nf-κB) and cytokines (such as TNF-α), thereby exerting anti-inflammatory effects. D-chiro-Inositol may be used in the study of liver cirrhosis, breast cancer, type 2 diabetes, and polycystic ovary syndrome.
    D-chiro-Inositol (Standard)
  • HY-B0380AR
    Trimebutine maleate (Standard)
    		Inhibitor
    Trimebutine maleate (Standard) is the analytical standard of Trimebutine maleate (HY-B0380A). This product is intended for research and analytical applications. Trimebutine maleate is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine maleate inhibits L-type Ca2+ channels and large-conductance calcium-activated potassium channels (BKCa channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine maleate 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 maleate also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine maleate also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS).
    Trimebutine maleate (Standard)
  • HY-N0773R
    Isovitexin (Standard)
    		Inhibitor
    Isovitexin (Standard) is the analytical standard of Isovitexin. This product is intended for research and analytical applications. Isovitexin is a flavonoid isolated from passion flower, Cannabis and, and the palm, possesses anti-inflammatory and anti-oxidant activities; Isovitexin acts like a JNK1/2 inhibitor and inhibits the activation of NF-κB.
    Isovitexin (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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