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-N6673
    Okanin
    Inhibitor 99.98%
    Okanin, effective constituent of the flower tea Coreopsis tinctoria, attenuates LPS-induced microglial activation through inhibition of the TLR4/NF-κB signaling pathways.
    Okanin
  • HY-15122A
    Sinomenine hydrochloride
    Inhibitor 99.89%
    Sinomenine hydrochloride (Cucoline hydrochloride), an alkaloid extracted from Sinomenium acutum, is a blocker of the NF-κB activation. Sinomenine also is an activator of μ-opioid receptor.
    Sinomenine hydrochloride
  • HY-N0108
    Physcion
    Inhibitor 99.40%
    Physcion (Parietin), an anthraquinone derivative derived from the traditional Chinese medicine rhubarb, is an effective oral active 6-phosphogluconate dehydrogenase inhibitor with blood-brain barrier permeability, with IC50 and Kd values of 38.5 μM and 26.0 μM, respectively. Additionally, Physcion is an inhibitor of the <>bTLR4/NF-κB signaling pathway, exhibiting anti-inflammatory, antibacterial, and anticancer effects, and can induce Apoptosis and Autophagy in cancer cells.
    Physcion
  • HY-148013
    K284-6111
    Inhibitor 99.94%
    K284-6111 is a high-affinity and orally active CHI3L1 inhibitor, and inhibits CHI3L1 expression. K284-6111 inhibits ERK and NF-κB pathway. K284-6111 suppresses nuclear translocation of p50 and p65, and phosphorylation of IκB. K284-6111 improves memory dysfunction by alleviating amyloidogenesis and neuroinflammation, with the reduction of inflammatory proteins (eg: iNOS, COX-2, GFAP, and Iba-1). K284-6111 reduces atopic-like skin inflammation and inhibits LPS (HY-D1056) -induced liver injury. K284-6111 can be used for the study of Alzheimer's diseases and sepsis like hepatic injury.
    K284-6111
  • HY-P99143
    Anti-Mouse NK1.1 Antibody (PK136)
    Inhibitor 98.57%
    Anti-Mouse NK1.1 Antibody (PK136) is an anti-mouse NK1.1 IgG2a monoclonal antibody. Anti-Mouse NK1.1 Antibody (PK136) can deplete natural killer (NK) cells. Anti-Mouse NK1.1 Antibody (PK136) inhibits the JAK-STAT and NF-κB signaling pathways. Anti-Mouse NK1.1 Antibody (PK136) can be used for research on inflammation conditions such as non-alcoholic steatohepatitis (NASH).
    Anti-Mouse NK1.1 Antibody (PK136)
  • HY-N0298
    Stachydrine
    Inhibitor 99.93%
    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
  • HY-N0390S
    L-Glutamine-15N
    Inhibitor 99.6%
    L-Glutamine-15N is the 15N-labeled L-Glutamine (HY-N0390). L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na+-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.
    L-Glutamine-<sup>15</sup>N
  • HY-N0716A
    Berberine hemisulfate
    Inhibitor 99.63%
    Berberine hemisulfate is the hemisulfate form of Berberine (HY-N0716). Berberine hemisulfate is an alkaloid isolated from the Chinese herbal medicine Huanglian. Berberine hemisulfate exhibits anti-inflammatory, antibiobic, antitumor, cardiovascular protective and neuroprotective activity.
    Berberine hemisulfate
  • HY-B0765
    Dehydroepiandrosterone sulfate sodium
    Inhibitor 99.96%
    Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) sodium salt is a neurosteroid and the main secretion product of the adrenal gland. Dehydroepiandrosterone sulfate sodium salt has both non-competitive antagonist activity of GABAA receptor and agonist activity of σ1 receptor. Dehydroepiandrosterone sulfate sodium salt can partially penetrate the blood-brain barrier, inhibit GABAA receptor-mediated chloride influx, enhance NMDA receptor activity through σ1 receptors, exert anti-inflammatory, anti-glucocorticoid and antidepressant effects, and increase convulsive sensitivity. Dehydroepiandrosterone sulfate sodium salt participates in neuroprotection, neurite growth regulation and catecholamine secretion regulation, and can be used in the study of depression, post-traumatic stress disorder (PTSD), Alzheimer's disease, etc. Dehydroepiandrosterone sulfate sodium salt may also be a biomarker for cardiovascular disease mortality, and its concentration is independently and negatively correlated with mortality.
    Dehydroepiandrosterone sulfate sodium
  • HY-N0633
    Muscone
    Inhibitor 98.0%
    Muscone is the main active monomer of traditional Chinese medicine musk. Muscone inhibits NF-κB and NLRP3 inflammasome activation. Muscone remarkably decreases the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), and ultimately improves cardiac function and survival rate.
    Muscone
  • HY-100594
    EUK-134
    Inhibitor 98.27%
    EUK-134, a synthetic superoxide dismutase and catalase mimetic, protects rat kidneys from ischemia-reperfusion-induced damage. EUK-134 is a superoxide dismutase (SOD) mimetics (SODm) with catalase activity. EUK-134 is a mitoprotective antioxidant. EUK-134 reduces the expression of NF-κB, MDA level, and protein carbonylation in H9C2 cells.
    EUK-134
  • HY-134240
    L-Threonic acid magnesium
    Inhibitor ≥99.0%
    L-Threonic acid magnesium (Magnesium L-threonate) is the enantiomer of Threonic acid and the metabolite of vitamin C (HY-B0166). L-Threonic acid magnesium is a magnesium supplementation, that improves the brain magnesium concentration, inhibits the activation of TNF-α/NF-κB signaling pathway. L-Threonic acid magnesium can be used in research of Alzheimer’s disease. L-Threonic acid magnesium is orally active.
    L-Threonic acid magnesium
  • HY-P99014
    Cusatuzumab
    Inhibitor 98.87%
    Cusatuzumab (ARGX-110) is a selective competitive blocker targeting CD70 (with an equilibrium dissociation constant of 17 pM for binding to human CD70). Cusatuzumab also possesses enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity. It is a humanized IgG1 monoclonal antibody, artificially synthesized through humanization and genetic engineering modifications (CH2 region mutation to enhance effector function). Cusatuzumab has a dual mechanism of action: firstly, it competitively blocks the interaction between CD70 and CD27, inhibiting the CD27-NF-κB signaling pathway, reducing regulatory T cell (Treg) activation and tumor cell proliferation; secondly, by enhancing binding to FcγRIIIa, it mediates ADCC and antibody-dependent cellular phagocytosis (ADCP), directly lysing CD70-positive tumor cells. Cusatuzumab can efficiently eliminate leukemia stem cells (LSCs), induce tumor cell differentiation and apoptosis, restore immune surveillance, and target CD70-positive tumors. Cusatuzumab is used in the study of acute myeloid leukemia (AML).
    Cusatuzumab
  • HY-119970
    Helenalin
    Inhibitor 99.92%
    Helenalin is an anti-inflammatory sesquiterpene lactone. Helenalin selectively inhibits transcription factor NF-κB by directly targeting p65. Helenalin has alkylating activity, targets the cysteine sulfhydryl groups in the p65 subunit of NF-κB, thereby inhibits its DNA binding.
    Helenalin
  • HY-N0652
    2,3,5,4'-Tetrahydroxystilbene 2-O-β-D-glucoside
    Inhibitor 99.91%
    2,3,5,4'-Tetrahydroxystilbene 2-O-β-D-glucoside isolats from the roots of Polygonaceae species, inhibits the formation of 5-HETE, HHT and thromboxane B2. 2,3,5,4'-Tetrahydroxystilbene 2-O-β-D-glucoside has hypotensive, anti-ageing, anti-inflammatory, hypolipidemic, cardioprotective, and neuroprotective actions.
    2,3,5,4'-Tetrahydroxystilbene 2-O-β-D-glucoside
  • HY-113556
    Sappanone A
    Inhibitor 99.87%
    Sappanone A is an orally active homoisoflavone found in sappan L. Sappanone A is a PDE4 and NF-κB inhibitor with anti-inflammatory and antioxidant effect. Sappanone A induces HO-1 expression through activation of Nrf2 pathway. Sappanone A also inhibits RANKL-induced osteoclastogenesis. Sappanone A has great potential in the research of inflammation-related and cardiovascular .
    Sappanone A
  • HY-W145499
    Zinc Gluconate
    Inhibitor 98.0%
    Zinc Gluconate is a zinc supplement in the form of a gluconate salt, which plays a role in various physiological processes such as immune function, wound healing, and olfaction. Zinc Gluconate has a LD50 of 39.6 mg/kg in mice (Tail vein injection). Zinc Gluconate can be used in the research of inflammation, zinc deficiency, colds, cancer, and nutritional supplements.
    Zinc Gluconate
  • HY-N0474
    Tyrosol
    Inhibitor 99.93%
    Tyrosol is a derivative of phenethyl alcohol. Tyrosol attenuates pro-inflammatory cytokines from cultured astrocytes and NF-κB activation. Anti-oxidative and anti-inflammatory effects.
    Tyrosol
  • HY-116035
    Nimbolide
    Inhibitor 99.79%
    Nimbolide is a triterpene compound that can be isolated from neem (Azadirachta indica), possesses anticancer and antiproliferative activity. Nimbolide induces tumor cell apoptosis by inhibiting NF-κB and CDK4/CDK6 kinase. Nimbolide suppresses the Wnt, PI3K-Akt, MAPK and JAK-STAT signaling pathways.
    Nimbolide
  • HY-12220
    MM-102
    Inhibitor 99.09%
    MM-102 (HMTase Inhibitor IX) is a cell-permeable and tightly binding inhibitor of MLL1-WDR5 interaction (IC50=2.4 nM). MM-102 can specifically inhibit the growth and induce apoptosis of leukemia cells containing MLL1 fusion protein, and reduce renal fibrosis and inflammation in mice with ischemia-reperfusion injury. In addition, MM-102 also acts as an H3K4 histone methyltransferase inhibitor to improve the development of porcine somatic cell nuclear transfer (SCNT) embryos.
    MM-102
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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