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-N0513
    Loganic acid
    Inhibitor 99.05%
    Loganic acid is an iridoid isolated from cornelian cherry fruits. Loganic acid inhibits NF-κB signaling pathway, activates Nrf2 signaling pathway, exhibits anti-inflammatory activity. Loganic acid can modulate diet-induced atherosclerosis and redox status. Loganic acid has strong free radical scavenging activity and remarkable cyto-protective effect against heavy metal mediated toxicity. Loganic acid is orally active.
    Loganic acid
  • HY-N2453
    Convallatoxin
    Inhibitor 99.72%
    Convallatoxin is a cardiac glycoside isolated from Adonis amurensis Regel et Radde. Convallatoxin ameliorates colitic inflammation via activation of PPARγ and suppression of NF-κB. Convallatoxin is a P-glycoprotein (P-gp) substrate and recognized Val982 as an important amino acid involved in its transport. Convallatoxin is an enhancer of ligand-induced MOR endocytosis with high potency and efficacy. Anti-inflammatory and anti-proliferative properties.
    Convallatoxin
  • HY-Y1117
    Melamine
    Activator 99.97%
    Melamine is an orally active inducer of Apoptosis. Melamine induces animal disease models. Melamine affects the activity of Sertoli cell and can be used for research on male reproductive function. Melamine also has neurotoxicity and nephrotoxicity. Melamine induces cognitive impairment and acute kidney injury models. Melamine can also be used to induce bladder cancer and urinary stone models.
    Melamine
  • HY-N2491
    Deoxyelephantopin
    Inhibitor 99.87%
    Deoxyelephantopin, a natural bioactive sesquiterpene lactone from Elephantopus scaber, has shown promising anticancer effects against a broad spectrum of cancers. Deoxyelephantopin inhibits NF-κB, MAPK, PI3K/Akt, and β-catenin signaling.
    Deoxyelephantopin
  • HY-134353B
    ADP-β-S trilithium
    Activator
    ADP-β-S (Adenosine 5'-(β-thiodiphosphate)) trilithium is a non-hydrolyzable ADP analog and a P2Y12 receptor agonist. ADP-β-S trilithium activates the P2Y12 receptor in microglia, thereby triggering downstream inflammatory signaling pathways. ADP-β-S trilithium activates P2Y purinergic receptors in rat pancreatic β cells and enhances glucose-induced insulin secretion. ADP-β-S trilithium can be used in the research of diseases such as inflammation and diabetes.
    ADP-β-S trilithium
  • HY-W013812
    Ethyl linoleate
    Inhibitor 99.72%
    Ethyl linoleate (Linoleic Acid ethyl ester) is an orally active unsaturated fatty acid. Ethyl linoleate inhibits the Akt/GSK3β/β-catenin signaling pathway and the activation of NF-κB. Ethyl linoleate induces heme oxygenase-1 and inhibits tyrosinase. Ethyl linoleate has whitening and anti-inflammatory effects. Ethyl linoleate promotes compound absorption. Ethyl linoleate has a significant influence on atherosclerosis. Ethyl linoleate is used in the research of inflammatory diseases. Ethyl linoleate can be used in cosmetics
    Ethyl linoleate
  • HY-N8290
    Lactupicrin
    Inhibitor 99.62%
    Lactupicrin (Lactucopicrin) exhibits analgesic, sedative, antimalarial activities and atheroprotective effect. Lactupicrin inhibits acetylcholinesterase (AChE) with an IC50 of 150.3 μM. Lactupicrin is an orally active characteristic bitter sesquiterpene lactone.
    Lactupicrin
  • HY-N0735
    Phellodendrine chloride
    Inhibitor 99.68%
    Phellodendrine chloride is an orally active plant alkaloid. Phellodendrine chloride inhibits the proliferation of KRAS-mutated pancreatic cancer cells by suppressing macropinocytosis and glutamine metabolism, inducing ROS accumulation and mitochondrial apoptosis. Phellodendrine chloride promotes autophagy by activating the AMPK/mTOR pathway, alleviating intestinal damage in ulcerative colitis. Phellodendrine chloride can alleviate gouty arthritis by inhibiting the IL-6/STAT3 signaling pathway. Phellodendrine chloride suppresses allergic reactions by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequent downstream MAPK and NF-κB signaling. Phellodendrine chloride inhibits the AKT/NF-κB pathway and down-regulates the expression of COX-2, thereby protecting zebrafish embryos from oxidative stress. Phellodendrine chloride has an anti-major depressive disorder (MDD) effect by down-regulating CHRM1, HTR1A, and the PI3K/Akt signaling pathway.
    Phellodendrine chloride
  • HY-W015490
    1,4-Naphthoquinone
    Inhibitor 99.97%
    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
  • HY-107802
    Breviscapine
    Inhibitor 99.13%
    Breviscapine (Breviscapinun) is a flavonoid compound with antioxidant, anti-inflammatory, anti-fibrotic, and neuroprotective activities. Breviscapine ameliorates cerebral ischemia/reperfusion injury and vascular dementia, and inhibits the formation of postoperative abdominal adhesions. The mechanism of action of Breviscapine involves the regulation of oxidative stress, inflammatory cytokines, signaling pathways such as TGF-β/Smad, and cellular calcium overload. Breviscapine is used for research on diseases including cardiovascular and cerebrovascular diseases.
    Breviscapine
  • HY-N0802
    Tenuigenin
    Inhibitor 99.92%
    Tenuigenin is a major active component isolated from the root of the Chinese herb Polygala tenuifolia. Tenuigenin protects against S.aureus-induced pneumonia by inhibiting NF-κB activation. Tenuigenin has anti-inflammatory effect.
    Tenuigenin
  • HY-N0648
    Monotropein
    Inhibitor 99.80%
    Monotropein is an iridoid glycoside that can be isolated from the roots of Morinda officinalis. Monotropein inhibits the expression of inflammatory mediators in dextran sulfate sodium (DSS)-induced colitis mouse model. Monotropein exerts protective effects against IL-1β-induced apoptosis and catabolic responses on osteoarthritis chondrocytes. Monotropein has cartilage protective activity. Monotropein can alleviate Cisplatin (HY-17394)-induced acute kidney injury by inhibiting oxidative damage, inflammation and apoptosis through activation of Nrf2/HO-1 pathway and inhibition of NF-κB signaling. Monotropein can be studied in research for osteoarthritis, acute kidney injury and acute lung injury.
    Monotropein
  • HY-N0758
    Barlerin
    99.82%
    Barlerin (8-O-Acetyl shanzhiside methyl ester) is an iridoid glucoside isolated from the leaves of Lamiophlomis rotata Kudo, a Chinese folk medicinal plant in Xi-zang. Barlerin (8-O-Acetyl shanzhiside methyl ester) could inhibt NF-κB.
    Barlerin
  • HY-122308
    Militarine
    Inhibitor 99.94%
    Militarine is a plant growth inhibitor and anti-inflammatory agent. Militarine inhibits the elongation of radicles and hypocotyls in seedlings of lettuce, Italian ryegrass and timothy grass. Militarine alleviates PM2.5-induced inflammatory injury and inhibits cell migration in human alveolar epithelial A549 cells by inhibiting the NF-κB signaling pathway, reducing oxidative stress and the release of inflammatory factors. Militarine can be used in studies related to PM2.5-induced pulmonary diseases.
    Militarine
  • HY-N2125
    Parishin C
    99.24%
    Parishin C is a brain-penetrant major bioactive component found in Gastrodia elata Blume. Parishin C is a 5-HT1A receptor agonist with an EC50 of 34 nM. Parishin C has antipsychotic and neuroprotective effects. Parishin C protects against Aβ-induced long-term potentiation damage and NMDA receptor current impairment. Parishin C reduces oxidative stress, pro-inflammatory cytokine levels, caspase activity, brain water content, and cerebral infarct volume; increases antioxidant enzyme activity and BDNF levels; improves nerve function and histopathological brain damage. Parishin C attenuates phencyclidine-induced immobility time increases, sociability deficits, and visual recognition memory impairment. Parishin C can be used for the research of ischemic stroke, Alzheimer's disease, and schizophrenia-like psychosis.
    Parishin C
  • HY-N3519
    Platycodin D3
    Inhibitor 98.91%
    Platycodin D3 is a triterpenoid saponin that can be found in Platycodon grandiflorum. Platycodin D3 exhibits multiple activities including anti-inflammation, regulation of airway mucus secretion, improvement of asthmatic airway inflammation and remodeling, and inhibition of hepatitis C virus (HCV) replication. The IC50 value of Platycodin D3 against HCV NS5B RNA-dependent RNA polymerase is 8 μg/mL. Platycodin D3 can be used in studies related to asthma, hepatitis C virus infection and inflammatory diseases.
    Platycodin D3
  • HY-N0657
    Pinoresinol Diglucoside
    99.84%
    Pinoresinol Diglucoside is an orally active lignan with multifunctional bioactivity. Pinoresinol Diglucoside interacts with targets including ALB, HIF1A, GSK3B, BCL2, MARK3, IL6, NF-κB p65, Nrf2, HO-1, and TLR4, and modulates pathways including PI3K-Akt, estrogen, MAPK, Rap1, AKT/mTOR/NF-κB, and TGF-β1/Smads. Pinoresinol Diglucoside regulates osteogenesis, bone resorption, oxidative stress, inflammation, apoptosis, ferroptosis, ferritinophagy, cardiac fibrosis, and vasorelaxation. Pinoresinol Diglucoside can be used for the research of osteoporosis, ischemia/reperfusion-induced brain injury, Alzheimer’s disease, myocardial ischemia-reperfusion injury, chondrodysplasia, diabetic cardiomyopathy, cardiac hypertrophy, hypertension, cisplatin-induced hearing loss, atherosclerotic cardiovascular diseases, and disuse osteoporosis.
    Pinoresinol Diglucoside
  • HY-N2149A
    Tomatidine hydrochloride
    Inhibitor 99.70%
    Tomatidine hydrochloride acts as an anti-inflammatory agent by blocking NF-κB and JNK signaling. Tomatidine hydrochloride activates autophagy either in mammal cells or C elegans.
    Tomatidine hydrochloride
  • HY-113402A
    Gamma-glutamylcysteine TFA
    Inhibitor
    Gamma-glutamylcysteine TFA (γ-Glu-Cys TFA) is an orally active, blood-brain barrier permeable dipeptide. Gamma-glutamylcysteine TFA activates AMPK, SIRT1, IL-4/STAT6, AC/cAMP/PI3K, IGF-1R/IRS1/PI3K, and Nrf2 signaling pathways; it inhibits NF-κB, JAK1/STAT1/3, MAPKs, cadmium-induced p38 MAPK, JNK, and PI3K/Akt signaling pathways. Gamma-glutamylcysteine TFA regulates macrophage polarization, modulates the trafficking of CD36 and GLUT4, induces glutathione synthesis, improves metabolic dysfunction, reduces lipid deposition, ameliorates glucose homeostasis, inhibits apoptosis (Apoptosis), stabilizes mitochondria, suppresses lipid peroxidation, iron accumulation and ferroptosis (Ferroptosis), reduces ds-HMGB1 levels, reverses mechanical hyperalgesia, and alleviates hepatic lipid droplet formation. Gamma-glutamylcysteine TFA is applicable to research related to inflammatory bowel disease, type 2 diabetes, cadmium-induced neurotoxicity, Alzheimer's disease, cerebral ischemia/reperfusion injury, neuropathy, and alcoholic liver disease.
    Gamma-glutamylcysteine TFA
  • HY-N6263
    EGCG Octaacetate
    Inhibitor 98.57%
    EGCG Octaacetate (AcEGCG) is a proagent of Green tea epigallocatechin-3-gallate (EGCG). EGCG Octaacetate decreases the proinflammatory mediator levels by down-regulating of PI3K/Akt/NFκB phosphorylation and p65 acetylation. EGCG octaacetate is the potential antibacterial compound for gram-positive bacteria (GPB) and gram-negative bacteria (GNB). EGCG Octaacetate exhibits antioxidant, anti-angiogenesis, anti-inflammatory and antitumor activities.
    EGCG Octaacetate
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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