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-112671
    CDDO-dhTFEA
    Inhibitor 99.71%
    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
  • HY-121508
    (E/Z)-IT-603
    Inhibitor 99.91%
    (E/Z)-IT-603 is a mixture of E-IT-603 and Z-IT-603 (IT-603). (E/Z)-IT-603 is also an IĸBα/c-Rel inhibitor. IT-603 is a c-Rel inhibitor with an IC50 of 3 μM. IT-603 has anti-tumor activity. (E/Z)-IT-603 is a promising modulator of T-cell responses in the context of graft-versus-host disease (GVHD) and malignant diseases.
    (E/Z)-IT-603
  • HY-N0665
    Specnuezhenide
    Inhibitor 99.52%
    Specnuezhenide ((8E)-Nuezhenide) is isolated from the fruits of?Ligustrum lucidum. Specnuezhenide ((8E)-Nuezhenide) can inhibit IL-1β-induced inflammation in chondrocytes via inhibition of NF-κB and wnt/β-catenin signaling. Specnuezhenide ((8E)-Nuezhenide) exerts anti-inflammatory effects in a rat model of osteoarthritis (OA).
    Specnuezhenide
  • HY-B2082
    Fursultiamine
    Inhibitor 99.92%
    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-101259
    BMS-195614
    Inhibitor 99.5%
    BMS-195614 (BMS 614) is an orally active neutral RARα-selective antagonist with a Ki of 2.5 nM. BMS-195614 restores the expression of Bcl2. BMS-195614 inhibits the transactivation of NF-κB, AP-1 and PPAR. BMS-195614 downregulates the expression of IL-6 and VEGF. BMS-195614 reduces blue light-induced phototoxicity and inhibits cell migration. BMS-195614 modulates inflammation and angiogenesis.
    BMS-195614
  • HY-N2485
    4'-Methoxyresveratrol
    Inhibitor 99.48%
    4'-Methoxyresveratrol (4'-O-Methylresveratrol) is a polyphenol derived from Dipterocarpaceae, with antiandrogenic, antifungal and anti-inflammatory activities. 4'-Methoxyresveratrol alleviates AGE-induced inflammation through suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation.
    4'-Methoxyresveratrol
  • HY-N2149A
    Tomatidine hydrochloride
    Inhibitor 99.58%
    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-N0809
    Sesamolin
    Inhibitor 99.78%
    Sesamolin, isolated from Sesamum indicum, has antioxidative activity, Sesamolin inhibits lipid peroxidation and shows neuroprotection effect. Sesamolinl potently inhibits MAPK cascades by preventing phosphorylation of JNK, p38 MAPKs, and caspase-3 but not ERK-MAPK expression. Sesamolin is orally active.
    Sesamolin
  • HY-101364
    CHPG
    Activator 99.51%
    CHPG is a selective mGluR5 agonist, and attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells. CHPG protects against traumatic brain injury (TBI) in vitro and in vivo by activation of the ERK and Akt signaling pathways.
    CHPG
  • HY-B0072
    Tropisetron
    Inhibitor 98.72%
    Tropisetron (SDZ-ICS-930 free base) is an orally active anti-inflammatory and antiemetic agent. Tropisetron is 5-HT3R antagonists with a Ki of 5.3 nM. Tropisetron is also a partial agonist of α7 nicotinic receptor (α7 nAChR) with an EC50 of 1.3 μM. In addition, Tropisetron has antitumor and neuroprotective effects.
    Tropisetron
  • HY-49444
    EN450
    Degrader 99.28%
    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-N5060
    Estragole
    Modulator 98.58%
    Estragole (4-Allylanisole) is a relatively nontoxic volatile terpenoid ether and major component of the essential oil from many plants. Estragole significantly triggers Apoptosis, suppresses LPS-induced intracellular ROS production. Estragole activats Nrf-2 and regulates NF-κB. Estragole has anti-toxoplasma, anti-inflammatory, anti-edema, antioxidant and immunomodulatory properties. Estragole blocks DRG neuron excitability. Estragole has improves gastric ulcer activity.
    Estragole
  • HY-N2055
    Kaempferol 3-O-sophoroside
    Inhibitor 99.84%
    Kaempferol 3-O-sophoroside is an orally active derivative of Kaempferol. It exhibits anti-inflammatory, analgesic, and antidepressant effects. Kaempferol 3-O-sophoroside is an inhibitor of the cell surface receptor toll-like receptor (TLR) 2/4 for High mobility group box 1 (HMGB1), and it also exerts anti-inflammatory effects by blocking the activation of NF-κB expression and the production of TNF-α. Kaempferol 3-O-sophoroside promotes the production of brain-derived neurotrophic factor (BDNF) and enhances autophagy by binding to AMP-activated protein kinase (AMPK), thereby exerting antidepressant effects. Kaempferol 3-O-sophoroside holds promise for research in the fields of inflammation and neurodegenerative diseases.
    Kaempferol 3-O-sophoroside
  • HY-N0513
    Loganic acid
    Inhibitor 99.93%
    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-N2086
    Ethyl palmitate
    Inhibitor 99.09%
    Ethyl palmitate (Ethyl hexadecanoate) is a CHIKV virus inhibitor with an EC50 value of 0.0068 μM. Ethyl palmitate can reduce levels of TNF-α, IL-6, and NF-κB in endotoxemic rats, showing anti-inflammatory activity.
    Ethyl palmitate
  • HY-N1363
    Royal Jelly acid
    Inhibitor 99.42%
    Royal Jelly Acid ((E)-Queen Bee Acid) is a major fatty acid found in royal jelly with oral bioavailability, exhibiting anti-inflammatory, anticancer, antimalarial, antiprotozoal, and neuroregulatory activities. Royal Jelly Acid can be used for research in various fields, including cancer, infections, immune inflammation, and neurological diseases.
    Royal Jelly acid
  • HY-N0617
    Sanggenon C
    Inhibitor 98.50%
    Sanggenon C, a flavonoid, exerts protective effects against cardiac hypertrophy and fibrosis via suppression of the calcineurin/NFAT2 pathway. Sanggenon C inhibits mitochondrial fission to induce apoptosis by blocking the ERK signaling pathway. Sanggenon C inhibits inducible nitric oxide synthase expression in RAW264.7 cells, and TNF-α-stimulated cell adhesion and VCAM-1 expression, by suppressing NF-κB activity. Sanggenon C possesses antioxidant, anti-inflammatory and antitumor activities.
    Sanggenon C
  • HY-10072
    SPC 839
    Inhibitor 99.86%
    SPC 839 (compound 10) is an orally active inhibitor of AP-1 and NF-kB mediated transcriptional activation with IC50 of 0.008 μM.
    SPC 839
  • HY-N0041
    Ginsenoside Rb3
    Inhibitor 99.12%
    Ginsenoside Rb3 is extracted from steamed Panax ginseng C. A. Meyer. Ginsenoside Rb3 exhibits inhibitory effect on TNFα-induced NF-κB transcriptional activity with an IC50 of 8.2 μM in 293T cell lines. Ginsenoside Rb3 also inhibits the induction of COX-2 and iNOS mRNA.
    Ginsenoside Rb3
  • HY-N0492S
    α-Lipoic Acid-d5
    Inhibitor
    α-Lipoic Acid-d5 is the deuterium labeled α-Lipoic Acid. α-Lipoic Acid is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes. α-Lipoic Acid inhibits NF-κB-dependent HIV-1 LTR activation[1][2][3]. α-Lipoic Acid induces endoplasmic reticulum (ER) stress-mediated apoptosis in hepatoma cells[4].
    α-Lipoic Acid-d<sub>5</sub>
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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