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. 상품명 효과 Purity Chemical Structure
  • HY-W229874
    EN106
    		Inhibitor 99.92%
    EN106 is a potent inhibitor of FEMIB. EN106 is a cysteine-reactive covalent ligand. EN106 disrupts recognition of the key reductive stress substrate of FEM1B, FNIP1. EN106 reduces oxidative stress and rescues high glucose-induced impaired angiogenesis in HUVECs.
    EN106
  • HY-N2350
    Cynaropicrin
    		Inhibitor 99.79%
    Cynaropicrin is a sesquiterpene lactone which can inhibit tumor necrosis factor (TNF-α) release with IC50s of 8.24 and 3.18 μM for murine and human macrophage cells, respectively. Cynaropicrin also inhibits the increase of cartilage degradation factor (MMP13) and suppresses NF-κB signaling.
    Cynaropicrin
  • HY-N5142
    α-Terpineol
    		Inhibitor 99.74%
    α-Terpineol (with oral activity) can be found in Eucalyptus globulus Labill. α-Terpineol exhibits strong antimicrobial activity against periodontopathic and cariogenic bacteria.α-Terpineol possesses antifungal activity against T. mentagrophytes, and the activity might lead to irreversible cellular disruption. In addition, α-Terpineol exhibits antineuropathic and anti-inflammatory activities. α-Terpineol can be utilized in research related to diarrhea, neuropathic pain, infections, and inflammation.
    α-Terpineol
  • HY-W082785A
    L6H21
    		Inhibitor 99.19%
    L6H21, a Chalcone (HY-121054) derivative, is an orally active, potent and specific myeloid differentiation 2 (MD-2) inhibitor. L6H21 directly binds to MD-2 protein with a high affinity and low KD value of 33.3 μM, blocking the formation of the LPS-TLR4/MD-2 complex. L6H21 inhibits LPS-induced expression of TNF-α and IL-6 in RAW264.7 macrophages, with IC50 values of 6.58 and 8.59 μM, respectively. L6H21 can be used for alcoholic liver disease, metabolic disturbance and neuroinflammation research.
    L6H21
  • HY-B0072
    Tropisetron
    		Inhibitor 99.93%
    Tropisetron is an orally active 5-HT3R antagonist (Ki = 5.3 nM) as well as being a potent and selective α7 nicotinic partial agonist (EC50 = 1.3 μM). Tropisetron prevents phosphorylation and activation of the p38 MAPK. Tropisetron inhibits both IL-2 gene transcription and IL-2 synthesis in stimulated T cells. Tropisetron inhibits the binding to DNA and the transcriptional activity of NFAT and AP-1. Tropisetron is anti-inflammatory and antiemetic. Tropisetron has antitumor and neuroprotective effects. Tropisetron can be studied in research for diseases including hemorrhagic cystitis, chronic joint inflammation, lung cancer and chronic cerebral hypoperfusion.
    Tropisetron
  • HY-N0696
    Sipeimine
    		Inhibitor 98.57%
    Sipeimine (Imperialine) is an inhibitor targeting the PI3K/AKT/NF-κB pathway and NLRP3 inflammasome, which can competitively bind to PI3K and p65. Sipeimine inhibits PI3K/AKT phosphorylation, blocks NF-κB nuclear translocation and NLRP3 inflammasome activation. Sipeimine exerts anti-inflammatory activities, inhibits pyroptosis and ferroptosis, and protects the extracellular matrix. Sipeimine can reduce cartilage degradation and synovial inflammation in osteoarthritis and improve PM2.5-induced lung injury. Sipeimine is mainly used in the study of anti-inflammatory and degenerative diseases.
    Sipeimine
  • HY-N2055
    Kaempferol 3-O-sophoroside
    		Inhibitor 99.41%
    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-N1508
    Ecliptasaponin A
    		Inhibitor 99.81%
    Ecliptasaponin A is an orally active pentacyclic triterpenoid saponin. Ecliptasaponin A exerts anti-tumor activity by activating ASK1/JNK pathway, inducing apoptosis and autophagy in lung cancer cells. Ecliptasaponin A exerts anti-inflammatory/anti-fibrotic effects and protects the cardiovascular system by inhibiting the HMGB1/TLR4/NF-κB pathway, and the expression of COX-2 and MMP-9. Ecliptasaponin A can enhance SOD activity, reduce MDA levels, and alleviate oxidative stress damage. Ecliptasaponin A exerts chondroprotective effects by inhibiting the expression of MMP13 and regulating inflammatory factors. Ecliptasaponin A improves ovarian function and regulates sex hormones by upregulating the expression of ESR1 receptors.
    Ecliptasaponin A
  • HY-N2434
    [10]-Shogaol
    		Inhibitor 99.78%
    [10]-Shogaol is an orally active antioxidant. [10]-Shogaol can be extracted from ginger (Zingiber officinale). [10]-Shogaol1 inhibits COX-2 with an IC50 value of 7.5 μM. [10]-Shogaol inhibits the production of proinflammatory cytokines (IL-1β, IL-6). [10]-Shogaol inhibits NF-κB phosphorylation. [10]-Shogaol has anti-inflammatory effects. [10]-Shogaol has anticancer effects against Docetaxel (HY-B0011)-resistant prostate cancer. [10]-Shogaol exhibits larvicidal activity against L5 larvae of Angiostrongylus cantonensis.
    [10]-Shogaol
  • HY-N6031
    Dendrophenol
    		Inhibitor 99.93%
    Dendrophenol (Moscatilin) is a NF-κB inhibitor that inhibits inflammation. Dendrophenol exerts potent cytotoxic effect against tumor cells and induces cell cycle arrest and apoptosis. Dendrophenol has antitumor activity. In addition, Dendrophenol can inhibit vascular calcification by inhibiting the activation of WNT3/β-catenin.
    Dendrophenol
  • HY-N2450
    Sulforaphene
    		Inhibitor 99.78%
    Sulforaphene, isolated from radish seeds, exhibits an ED50 against velvetleaf seedlings approximately 2 x 10-4 M. Sulforaphene promotes cancer cells apoptosis and inhibits migration via inhibiting EGFR, p-ERK1/2, NF‐κB and other signals.
    Sulforaphene
  • HY-W006957
    N6-(2-Hydroxyethyl)adenosine
    		Inhibitor 99.85%
    N6-(2-Hydroxyethyl)adenosine is a purine nucleoside analog. N6-(2-Hydroxyethyl)adenosine inhibits NF-κB/Smad signaling pathway, exhibits anti-hyperglycemia, antioxidant, antitumor and anti-inflammatory and insecticidal activities. N6-(2-Hydroxyethyl)adenosine is orally active.
    N6-(2-Hydroxyethyl)adenosine
  • HY-105935
    Keracyanin chloride
    		Inhibitor 99.90%
    Keracyanin chloride inhibits NF-κB/FAK/MAPK signaling pathway. Keracyanin chloride exhibits antioxidant, anti-inflammatory and hypoglycemic effects, and is orally active.
    Keracyanin chloride
  • HY-N3945
    Glaucine
    		Inhibitor 99.57%
    Glaucine (O,O-Dimethylisoboldine) is an alkaloid extracted from Glaucium flavum that possesses various activities, including cough relief, bronchodilation, anti-inflammatory effects, analgesia, antipyretic properties, and anticancer effects. Glaucine acts as a selective and orally active inhibitor of phosphodiesterase 4 (PDE4), with a Ki of 3.4 µM in human bronchial tissues and polymorphonuclear leukocytes. Glaucine induces relaxation of human isolated bronchi by antagonizing calcium channels. Additionally, Glaucine inhibits the activation of NF-κB, leading to a reduction in the expression of the MMP-9 gene, thereby suppressing the migration and invasion of breast cancer cells. Therefore, Glaucine holds potential for research in asthma and breast cancer.
    Glaucine
  • HY-10227R
    Bortezomib (Standard)
    		Inhibitor
    Bortezomib (Standard) is the analytical standard of Bortezomib. This product is intended for research and analytical applications. Bortezomib (PS-341) is a reversible and selective proteasome inhibitor, and potently inhibits 20S proteasome (Ki=0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is the first proteasome inhibitor anticancer agent. Bortezomib can be used for the study of multiple myeloma (MM). Bortezomib effectively inhibits TREM2 expression in tumor-associated macrophages (TAMs).
    Bortezomib (Standard)
  • HY-18976
    UF010
    		99.83%
    UF010 is a selective inhibitor of class I HDAC. UF010 has cytotoxicity to cancer cells and reduces neuroinflammation in the hippocampus. UF010 can be used for the research of neurological diseases.
    UF010
  • HY-B0130A
    Perindopril erbumine
    		99.98%
    Perindopril erbumine is an angiotensin-converting enzyme inhibitor. Perindopril erbumine modulates NF-κB and STAT3 signaling and inhibits glial activation and neuroinflammation. Perindopril erbumine can be used for the research of Chronic Kidney Disease and high blood pressure.
    Perindopril erbumine
  • HY-N2477
    Taraxerol
    		Inhibitor 99.91%
    Taraxerol is isolated from Taraxacum mongolicum, and has anti-inflammtory and anti-cancer effects. Taraxerol attenuates acute inlammation through inhibition of NF-κB signaling pathway. Taraxerol induces cell apoptosis.
    Taraxerol
  • HY-N0442
    5-O-Methylvisammioside
    		Inhibitor 99.90%
    5-O-Methylvisammioside (4'-O-β-D-Glucosyl-5-O-methylvisamminol) is an orally active natural chromone glycoside and multiple biological activities. 5-O-Methylvisammioside inhibits ferroptosis by activating the Nrf2/HO-1 signaling axis. 5-O-Methylvisammioside alleviates intestinal barrier damage by inhibiting the ROS/NF-κB/NLRP3 pathway. 5-O-Methylvisammioside exerts a protective effect against acute liver injury by reducing ALT/AST, decreasing inflammatory infiltration, and inhibiting IκB-α phosphorylation and NF-κB nuclear translocation. 5-O-Methylvisammioside blocks the HMGB1/RAGE/MEK/ERK signaling axis to exert anti-tumor and anti-angiogenic effects. 5-O-Methylvisammioside improves depression-like behaviors by inhibiting Src kinase and the NF-κB pathway.
    5-O-Methylvisammioside
  • HY-19696B
    Tauroursodeoxycholate dihydrate
    		Inhibitor 99.96%
    Tauroursodeoxycholate dehydrate is an orally active taurine conjugate of Ursodeoxycholic acid (HY-13771). Tauroursodeoxycholate dehydrate inhibits caspase-3/7, Apoptosis, IRE1α/TRAF2/NF-κB, prevents JNK phosphorylation, inhibits ROS generation, and activates Akt signaling. Tauroursodeoxycholate dehydrate prevents cataract formation, reduces renal tubular damage in type 2 diabetic mice, reduces I/R injury in liver, and inhibits intestinal inflammation and barrier disruption in nonalcoholic fatty liver disease.
    Tauroursodeoxycholate dihydrate
Cat. No. 상품명 / 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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