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-N2481
    Oroxylin A-7-O-glucuronide
    		Inhibitor 99.83%
    Oroxylin A-7-O-glucuronide (oroxyloside) is an orally active flavonoid glucuronide and metabolite of Oroxylin A (HY-N0560). Oroxylin A-7-O-glucuronide can be extracted from the dried root of Scutellaria baicalensis. Oroxylin A-7-O-glucuronide exhibits prolyl oligopeptidase inhibitory activity. Oroxylin A-7-O-glucuronide inhibits the JNK pathway, upregulates PPARγ, and inhibits NF-κB p65 nuclear translocation. Oroxylin A-7-O-glucuronide reduces cytokine (IL-1β, IL-6) production. Oroxylin A-7-O-glucuronide exhibits anti-angiogenic, anti-tumor (glioma, liver cancer), anti-inflammatory, and hepatoprotective activities.
    Oroxylin A-7-O-glucuronide
  • HY-W016969
    2-Undecanone
    		Inhibitor 99.90%
    2-Undecanone is an orally active organic ketone. 2-Undecanone exerts antibacterial effects by inhibiting bacterial chaperone systems and interfering with the refolding of heat-inactivated proteins. 2-Undecanone also ameliorates asthmatic inflammation and airway remodeling by blocking the NF-κB pathway, and activates the Nrf2 pathway to reduce oxidative damage and prevent lung cancer induced by Benzo[a]pyrene (HY-107377). 2-Undecanone can be used in research related to cancer, asthma and infections.
    2-Undecanone
  • HY-B2082
    Fursultiamine
    		Inhibitor 99.71%
    Fursultiamine is a vitamin B1 derivative, has anti-nociceptive and antineoplastic activity. Fursultiamine can be used for vitamin B1?deficiency, osteoarthritis (OA) and cancer research.
    Fursultiamine
  • HY-N6046
    Kamebakaurin
    		Inhibitor 99.64%
    Kamebakaurin is an orally active diterpenoid compound that can be isolated from Isodon excia (Maxin.). Kamebakaurin can inhibit NF-κB activation by directly targeting the DNA-binding activity of p50. Kamebakaurin can induce apoptosis and cell cycle arrest in tumor cells. Kamebakaurin has anti-inflammatory and anti-tumor activities.
    Kamebakaurin
  • HY-W001174
    2,5-Dihydroxyacetophenone
    		Inhibitor 99.95%
    2,5-Dihydroxyacetophenone, isolated from Rehmannia glutinosa, inhibits the production of inflammatory mediators in activated macrophages by blocking the ERK1/2 and NF-κB signaling pathways.
    2,5-Dihydroxyacetophenone
  • HY-N6066
    Praeruptorin E
    		Inhibitor 99.83%
    Praeruptorin E is an orally active pyranocoumarin compound. Praeruptorin E can be isolated from the dried roots of Peucedanum praeruptorum Dunn. Praeruptorin E reduces the expression of NF-κB. Praeruptorin E upregulates the expression of PXR and CYP3A4. Praeruptorin E inhibits Th2 cytokines, TNF-α, IL6, MPO, and blocks the Ca2+ slow channel. Praeruptorin E promotes pulmonary tissue repair and relaxes porcine coronary artery strips. Praeruptorin E protects mice from lipopolysaccharide- and hydrochloric acid-induced acute lung injury. Praeruptorin E can be used in studies related to asthma and acute lung injury.
    Praeruptorin E
  • HY-123856
    MY10
    		Inhibitor 99.87%
    MY10 is a potent and orally active receptor protein tyrosine phosphatase (RPTPβ/ζ) inhibitor. MY10 reduces NF-κB p65 expression. MY10 activates tyrosine phosphorylation of c-Met. MY10 prevents the alcohol-induced downregulation of Ptprz1 and Alk expression. MY10 attenuates binge-like ethanol consumption and ethanol reward. MY10 can be used in the study of neurological and vascular diseases.
    MY10
  • HY-P1847A
    IKKγ NBD Inhibitory Peptide TFA
    		98.77%
    IKKγ NBD Inhibitory Peptide TFA is a highly specific inhibitor NF-κB inhibitor. IKKγ NBD Inhibitory Peptide TFA acts by disrupting the interaction between IKKγ/NEMO-binding domain (NBD) with IKKα and IKKβ, thus blocking TNF-α-induced NF-kB activation. IKKγ NBD Inhibitory Peptide TFA could significantly suppresses inflammation and ameliorate the cerebral ischemia-induced neurological deficits.
    IKKγ NBD Inhibitory Peptide TFA
  • HY-19929
    Tanimilast
    		Inhibitor 99.71%
    Tanimilast (CHF-6001) is an orally active and selective phosphodiesterase 4 inhibitor (IC50=0.026 nM) with robust anti-inflammatory activity and suitable for topical pulmonary administration. Tanimilast increases cellular cAMP levels, and inhibits NF-κB signaling pathway. Tanimilast is used for the research of obstructive lung diseases.
    Tanimilast
  • HY-B0185S1
    Lidocaine-d10
    		Inhibitor 99.58%
    Lidocaine-d10 is the deuterium labeled Lidocaine. Lidocaine (Lignocaine) inhibits sodium channels involving complex voltage and using dependence. Lidocaine 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 is an amide derivative and has potential for the research of ventricular arrhythmia.
    Lidocaine-d<sub>10</sub>
  • HY-N4150
    Quercetagitrin
    		Inhibitor 98.34%
    Quercetagitrin (Quercetagetin-7-O-glucoside) is a natural product that can be isolated from the African marigold (Tagetes erecta). Quercetagitrin has anti-inflammatory activity. Quercetagitrin inhibits Tau accumulation. Quercetagitrin can reverse neuroinflammation and cognitive deficits in P301S-Tau transgenic mouse model through inhibiting NF-κB activation. Quercetagitrin is a dual-target inhibitor of PTPN6 (IC50 = 1 μM) and PTPN9 (IC50 = 1.7 μM). Quercetagitrin enhances glucose uptake by mature C2C12 myoblasts. Quercetagitrin can be studied in research for Alzheimer’s disease and type 2 diabetes.
    Quercetagitrin
  • HY-119720
    Neocryptotanshinone
    		Inhibitor 98.82%
    Neocryptotanshinone, a fatty diterpenoids from Salvia Miltiorrhiza, inhibits lipopolysaccharide-induced inflammation by suppression of NF-κB and iNOS signaling pathways.
    Neocryptotanshinone
  • HY-160477
    DC-SX029
    		Inhibitor 98.07%
    DC-SX029 is a potent SNX10 protein-protein interaction (PPI) inhibitor with oral activity with an estimated KD constant of ~0.935 μM by surface plasmon resonance (SPR). DC-SX029 blocks the SNX10-PIKfyve interaction, thereby decreased the TBK1/c-Rel signaling activation. DC-SX029 does not affect the protein level of SNX10. DC-SX029 has the potential for inflammatory bowel disease (IBD) research.
    DC-SX029
  • HY-N2132
    Flavokawain B
    		Inhibitor 99.99%
    Flavokawain B (Flavokavain B) is an orally active chalcone. Flavokawain B results in activation of caspase-9, -3 and -8, cleavage of PARP. Flavokawain B down-regulates Bcl-2 with concomitant increase in Bax level. Flavokawain B inhibits NF-κB, PI3K/Akt and MAPK signaling pathway. Flavokawain B exhibits Apoptotic effects. Flavokawain B inhibits MMP-9 and promotes ROS generation. Flavokawain B inhibits multiple tumors and inflammation.
    Flavokawain B
  • HY-49444
    EN450
    		Degrader 98.59%
    EN450 is a cysteine-reactive covalent molecular glue degrader targeting NF-κB. EN450 interacts with allosteric C111 in the E2 ubiquitin ligase UBE2D. EN450 induces the ternary complex formation between UBE2D and NFKB1. EN450 exerts its anti-proliferative effects through a Cullin E3 ligase and proteasome-dependent mechanism.
    EN450
  • HY-N2081
    Skimmianine
    		99.90%
    Skimmianine is an orally active furoquiniline alkaloid present mainly in the Rutaceae family. Skimmianine has analgesic, antispastic, sedative, and anti-inflammatory properties. Skimmianine inhibits acetylcholinesterase (AChE) (IC50 = 8.6 μg/mL). Skimmianine exhibits cytotoxicity against a variety of cancer cell lines and genotoxicity. Skimmianine has antioxidant and anti-inflammatory effects on ischemia-reperfusion (IR) injury. Skimmianine exerts anti-inflammatory effects through activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) pathway. Skimmianine is neuroprotective by targeting the NF-κB activation pathway to prevent neuroinflammation. Skimmianine inhibits the release of histamine, intracellular Ca2+ signaling and protein kinase C signaling.
    Skimmianine
  • HY-N7688
    Regaloside B
    		Inhibitor 99.90%
    Regaloside B is a phenylpropane. Regaloside B can be isolated from Lilium longiflorum. Regaloside B can inhibit the expression of VCAM-1, iNOS, and COX-2, with a p-p65/p-65 ratio. Regaloside B inhibits the mRNA of various chemokines and angiogenic factors (CXCL9, CXCL10, IL8, IDO). Regaloside B has anti-inflammatory activity. Regaloside B can be used for osteogenic differentiation research.
    Regaloside B
  • HY-N0390S5
    L-Glutamine-1-13C
    		Inhibitor 98.0%
    L-Glutamine-1-13C is the 13C-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-1-<sup>13</sup>C
  • HY-N0631
    Cornuside
    		Inhibitor 99.99%
    Cornuside is an iridoid glycoside with anti-allergic, anti-inflammatory, and neuroprotective activities. Cornuside exerts anti-allergic activity by downregulating the p38 MAPK, JNK, and NF-κB signaling pathways, and inhibits IgE-mediated histamine release from mast cells. Cornuside improves cognitive impairment in mice by inhibiting BACE1 activity (IC50 = 55.84 μg/mL) and enhancing ChAT activity. Cornuside inhibits LPS (HY-D1056)-induced inflammatory mediators, including iNOS, COX-2, PGE2, TNF-α, IL-6, and IL-1β, by suppressing NF-κB activation.
    Cornuside
  • HY-112671
    CDDO-dhTFEA
    		Inhibitor 99.64%
    CDDO-dhTFEA (RTA dh404) is a synthetic oleanane triterpenoid compound which potently activates Nrf2 and inhibits the pro-inflammatory transcription factor NF-κB. CDDO-dhTFEA restores hypertension (MAP), increases Nrf2 and expression of its target genes, attenuates activation of NF-κB and transforming growth factor-β pathways, and reduces glomerulosclerosis, interstitial fibrosis and inflammation in the chronic kidney disease (CKD) rats.
    CDDO-dhTFEA
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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