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-N9914R
    D-Psicose (Standard)
    		Inhibitor
    D-Psicose (Standard) is the analytical standard of D-Psicose (HY-N9914). This product is intended for research and analytical applications. D-psicose is an orally active rare sugar. D-psicose inhibits p38-MAPK phosphorylation and MCP-1 expression. D-psicose inhibits the AGEs/RAGE/NF-κB pathway. D-psicose protects pancreatic β-islets, improves hyperglycemia and high-fat diet-induced non-alcoholic fatty liver disease.
    D-Psicose (Standard)
  • HY-N0430A
    Coptisine Sulfate
    		Inhibitor 99.37%
    Coptisine Sulfate is an orally active and brain-penetrant alkaloid found in Coptis chinensis. Coptisine Sulfate is a reversible, uncompetitive IDO inhibitor with a Ki of 5.8 μM and an IC50 of 6.3 μM. Coptisine Sulfate suppresses neuroinflammation, reduces Aβ plaque burden and shows neuroprotective activity. Coptisine Sulfate shows anti-inflammation activity by blocking NF-κB, MAPK, and PI3K/Akt activation. Coptisine Sulfate inhibits cancer cells proliferation, induces DNA damage, G2/M phase cell cycle arrest, apoptosis, ROS production and mitochondrial dysfunction. Coptisine Sulfate inhibits Rho/ROCK pathway activation, reduces arrhythmia, limits cardiac injury marker release, reduces infarct size, and preserves cardiac function in rat myocardial ischemia/reperfusion models. Coptisine Sulfate downregulates HMGCR and upregulates LDLR and CYP7A1 to modulate cholesterol metabolism, reduces abnormal serum lipid levels, and promotes fecal bile acid excretion. Coptisine Sulfate be used for the research of cancer, hypercholesterolemia, Alzheimer’s disease, inflammatory disorders and cardiovascular disease.
    Coptisine Sulfate
  • HY-N7931
    Regaloside A
    		Inhibitor 99.64%
    Regaloside A, a phenylpropanoid, shows significant DPPH radical scavenging activity of 58.0% at 160 ppm. Regaloside A has anti-inflammatory activity.
    Regaloside A
  • HY-N0204
    Pulchinenoside A
    		Activator 98.81%
    Pulchinenoside A (Anemoside A3) is an orally active triterpenoid glycoside found in the root of Pulsatilla chinensis. Pulchinenoside A has amti-inflammation, antitumor, antidepressant, immunoregulatory and neuroprotective efrects. Pulchinenoside A activates NF-κB/MAPK signaling pathway. Pulchinenoside A can induce relaxing effect in rat renal arteries. Pulchinenoside A can be used for the researches of experimental autoimmune encephalomyelitis, breast cancer, depression and renovascular hypertension.
    Pulchinenoside A
  • HY-116538
    (10E,12Z)-Octadeca-10,12-dienoic acid
    		99.10%
    (10E,12Z)-Octadeca-10,12-dienoic acid (trans-10,cis-12 CLA2) is an orally active PPARα activator and inhibits adipocyte differentiation. (10E,12Z)-Octadeca-10,12-dienoic acid and its downstream metabolites have various antioxidant and antitumor activities. (10E,12Z)-Octadeca-10,12-dienoic acid can induce proinflammatory cytokines and chemokines, which would lead to decreased adipogenesis and insulin resistance in adipose tissue. (10E,12Z)-Octadeca-10,12-dienoic acid can affect many aspects of milk fat synthesis. (10E,12Z)-Octadeca-10,12-dienoic acid reduces expression of lipogenic enzymes and inhibits the desaturation of fatty acids. (10E,12Z)-Octadeca-10,12-dienoic acid can reduce lipoprotein lipase (LPL) activity in cultured 3T3-L1 adipocytes and enhance triacylglycerol release from these cells. (10E,12Z)-Octadeca-10,12-dienoic acid decreases the expression of hepatic stearoyl-CoA desatyrase mRNA in mice. (10E,12Z)-Octadeca-10,12-dienoic acid is associated with changes in mucosal NF-κB and Cyclin D1 protein levels in mice.
    (10E,12Z)-Octadeca-10,12-dienoic acid
  • HY-W100287
    Murrayafoline A
    		Inhibitor 99.73%
    Murrayafoline A is a carbazole alkaloid that can be extracted from Murraya tetramera. Murrayafoline A directly targets Specificity protein 1 (Sp1), thereby inhibiting NF-κB and MAPK signaling pathways. Murrayafoline a induces a G0/G1-phase arrest in platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells. Murrayafoline A attenuates the Wnt/β-catenin pathway by promoting the degradation of intracellular β-catenin proteins. Murrayafoline A enhances the contraction of rat ventricular myocytes and L-type calcium current by activating protein kinase C. Murrayafoline A inhibits LPS (HY-D1056)-induced neuroinflammation in vivo. Murrayafoline A can be used for the study of inflammation, vascular complications and colon cancer.
    Murrayafoline A
  • HY-121246
    Fluorofenidone
    		Inhibitor 99.78%
    Fluorofenidone (AKF-PD) is an orally active compound with anti-fibrotic, antioxidant, and anti-inflammatory pharmacological effects. Fluorofenidone downregulates the expression of ACSL4, upregulates GPX4 expression and inhibits the NF-κB signaling pathway to alleviate inflammation and fibrosis. Fluorofenidone ameliorates cholestasis and fibrosis by inhibiting hepatic Erk/-Egr-1 signaling and Tgfβ1/Smad pathway in mice. Fluorofenidone demonstrates protective effects against chronic lung injury in mice. Fluorofenidone can be used for the study of chronic obstructive pulmonary disease (COPD), pulmonary interstitial fibrosis (PIF) and non-small cell lung cancer (NSCLC).
    Fluorofenidone
  • HY-145801
    XT2
    		Inhibitor 99.60%
    XT2 is a potent, orally active, and selective inhibitor of NF-κB-inducing kinase (NIK) with an IC50 of 9.1 nM. XT2 suppresses CCl4-induced upregulation of ALT, a key biomarker of acute liver injury. XT2 also decreases immune cell infiltration into the injured liver tissue. XT2 has the potential for the research of liver inflammatory diseases. XT2 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    XT2
  • HY-N4225
    Aaptamine
    		Activator 99.71%
    Aaptamine is an alkaloid that can be isolated from the sponge Aaptos suberitoides. Aaptamine is a competitive antagonist of the α-adrenergic receptor, as well as an inhibitor of the proteasome and cholinesterase. Aaptamine is cytotoxic to tumor cells and can induce apoptosis, cell cycle arrest of tumor cells, and the expression of p21 through a p53-independent pathway. Aaptamine has multiple activities such as anti-tumor, antioxidant, antibacterial, and analgesic effects.
    Aaptamine
  • HY-N5025
    Bullatine A
    		Inhibitor 98.0%
    Bullatine A, a diterpenoid alkaloid, is a potent P2X7 antagonist. Bullatine A possesses anti-rheumatic, anti-inflammatory and anti-nociceptive effects. Bullatine A inhibits ATP-induced BV-2 cell death/apoptosis and P2X receptor-mediated inflammatory responses. Bullatine A suppresses glioma cell growth by targeting SIRT6. Bullatine A specifically attenuates pain hypersensitivity in rats. Bullatine A attenuates LPS (HY-D1056)-induced systemic inflammatory response by inhibiting the ROS/JNK/NF-κB pathway in mice. Bullatine A improves despair behavior in Chronic chronic social defeat stress (CSDS) mice. Bullatine A can be used for the study of inflammation, glioblastoma (GBM) and depression.
    Bullatine A
  • HY-W014223
    2,4′-Dihydroxybenzophenone
    		Inhibitor 98.00%
    2,4′-Dihydroxybenzophenone (Ultraviolet absorber UV-0) occupies the hydrophobic pocket of MD2 and blocks the dimerization of TLR4. 2,4′-Dihydroxybenzophenone inhibits the LPS induced mtROS production, and LPS induced inflammatory response by downregulating pro-inflammatory mediators and decreasing the expression of MyD88, p-IRAK4, and NF-κB. 2,4′-Dihydroxybenzophenone is also a UV absorber.
    2,4′-Dihydroxybenzophenone
  • HY-141582
    Ceramide 3
    		Inhibitor 98.0%
    Ceramide 3 (N-Stearoyl phytosphingosine) is an orally active major component of intercellular lipids in the stratum corneum of the skin, and belongs to the ceramide family. Ceramide 3 inhibits c-jun and NF-κB activation induced by Histamine (HY-B1204), and suppresses the expression of IL-4 and TNF-α. Ceramide 3 inhibits scratching behavior and vascular permeability in mice, and exhibits antihistamine effects in guinea pig ileum. Ceramide 3 improves skin barrier function, reduces transepidermal water loss, erythema and the number of circulating epidermal cells, and accelerates barrier repair of irritated or dysfunctional skin.
    Ceramide 3
  • HY-126066
    (-)-Syringaresinol
    		Inhibitor 99.93%
    (-)-Syringaresinol is an orally active isomer of syringaresinol (HY-N8307) found in Annona Montana. (-)-Syringaresinol exhibits antioxidant, anti-inflammatory, and anticancer activities. (-)-Syringaresinol can alleviate ulcerative colitis via the PI3K-Akt/MAPK/Wnt signaling pathway. (-)-Syringaresinol inhibits HL-60 cell proliferation by arresting the G1 phase and inducing apoptosis. (-)-Syringaresinol inhibits LPS (HY-D1056)-induced microglial activation by downregulating the NF-κB p65 signaling pathway and its interaction with ERβ, exerting anti-neuroinflammatory effects.
    (-)-Syringaresinol
  • HY-P10387
    RSM3
    		Modulator
    RSM3 is a METTL3-METTL14 complex inhibitor with a Kd of 3.10 μM for the METTL3-METTL14 complex. RSM3 reduces the m6A modification level of SLC31A1 and the global RNA methylation level. RSM3 upregulates programmed cell death-related genes, enhances cell apoptosis, inhibits pro-cancer signals and suppresses tumor growth. RSM3 is applicable to the research of preeclampsia and cancer.
    RSM3
  • HY-B0898
    Ceftiofur sodium
    		Inhibitor 98.02%
    Ceftiofur sodium is a cell wall synthesis inhibitor that targets bacterial penicillin-binding proteins (PBPs) and has anti-inflammatory effects in endotoxemia. Ceftiofur sodium exerts bactericidal effects by inhibiting the synthesis of bacterial cell wall peptidoglycan, leading to bacterial cell lysis. Ceftiofur sodium also inhibits the activation of NF-κB and MAPKs, thereby reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6.
    Ceftiofur sodium
  • HY-B1239
    Drofenine hydrochloride
    		98.10%
    Drofenine (Cycloadiphene; Hexahydroadiphenine) hydrochloride is an brain-penetrant antispasmodic agent. Drofenine hydrochloride is a Kv2.1 channel inhibitor with human IC50 of 9.53 μM. Drofenine hydrochloride is a butyrylcholinesterase (BChE) inhibitor with Ki of 0.003 mM, and is a TRPV3 activator. Drofenine hydrochloride blocks Kv2.1-dependent potassium efflux, inhibits Kv2.1/JNK/NF-κB and IkBa/NF-kB signaling, suppresses Kv2.1 mRNA/protein expression. Drofenine suppresses oligomeric Aβ-induced microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation, improves cognitive impairment, promotes neurite outgrowth. Drofenine hydrochloride induces calcium influx in keratinocytes and exert cytotoxicity against keratinocytes. Drofenine hydrochloride ameliorates diabetic peripheral neuropathy -like pathology. Drofenine hydrochloride can be used for the researches of Alzheimer's disease, diabetic peripheral neuropathy and smooth muscle spasm.
    Drofenine hydrochloride
  • HY-N3405
    Lariciresinol
    		Modulator 99.46%
    Lariciresinol is an orally active ingredient. Lariciresinol can be isolated from Arabidopsis thaliana. Lariciresinol inhibits α-glucosidase activity (IC50 of 6.97 μM; Ki of 0.046 μM). Lariciresinol dereases Bcl-2, upregulates Bax and induces Apoptosis. Lariciresinol regulates TGF-β and NF-κB pathways. Lariciresinol has antitumor activity against liver cancer, gastric cancer, and breast cancer. Lariciresinol shows antifungal activity and anti-diabetic activity.
    Lariciresinol
  • HY-N0670
    Tenacissoside H
    		Inhibitor 99.89%
    Tenacissoside H (Tenacissimoside C) is a compound found in Caulis Marsdeniae Tenacissimae. Tenacissoside H shows anti-inflammation, anti-tumor and neuroprotective effects. Tenacissoside H inhibits PI3K/Akt and NF-κB signaling pathway. Tenacissoside H inhibits cancer cells proliferation, S phase arrest, and inhibits tumor growyh in mice. Tenacissoside H promotes neurological recovery of ischemia-reperfusion injury in mice by inhibiting inflammation and apoptosis. Tenacissoside H can be used for the research of cancer, inflammation and neurological diseases, such as esophageal cancer and cerebral ischemia.
    Tenacissoside H
  • HY-N5083
    Saponarin
    		Inhibitor 99.95%
    Saponarin is an orally active flavonoid compound. Saponarin can be isolated from Gypsophila trichotoma. Saponarin inhibits ERK/p38, NF-κB and MAPK phosphorylation and activates AMPK. Saponarin reduces IL-1β and COX-2. Saponarin has antioxidant, anti-inflammatory, hepatoprotective, hypoglycemic and hypotensive effects. Saponarin improves sleep disorders.
    Saponarin
  • HY-N1956
    Rubiadin-1-methyl ether
    		Inhibitor 98.57%
    Rubiadin-1-methyl ether is a natural anthraquinone isolated from Morinda officinalis How, and inhibits osteoclastic bone resorption via inhibition on the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decrease in the nuclear translocation of p65.
    Rubiadin-1-methyl ether
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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