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-107665
    Ro 106-9920
    		Inhibitor ≥99.0%
    Ro 106-9920 is a potent inhibitor of NF-kappaB. Ro 106-9920 has the potential for the research of tumor and cancer diseases.
    Ro 106-9920
  • HY-N1965
    Gaultherin
    		Inhibitor 99.44%
    Gaultherin is an orally active non-steroidal anti-inflammatory agent. Gaultherin selectively inhibits NF-κB, MAPK, COX-2 (IC50 = 0.35 mg/mL), LOX (IC50 = 0.56 mg/mL) and HYAL (IC50=28.58 μg/mL) to exert anti-inflammatory, antipyretic and analgesic effects. Gaultherin exhibits modest direct antioxidant capacity, greater in cell-based models. Gaultherin does not affect COX-1 so that avoids the common gastrointestinal side effects of Aspirin (HY-14654).
    Gaultherin
  • HY-135808
    BIZ 114
    		Inhibitor ≥98.0%
    BIZ 114 (Example 11) is a fatty acid derivative and potent inhibits the TNF-α activated NF-κΒ pathway. BIZ 114 has the potential to prevent and / or treat ophthalmic disorders such as retinal degenerative disorders and ocular inflammatory diseases.
    BIZ 114
  • HY-B0185G
    Lidocaine (GMP)
    		Inhibitor
    Lidocaine (GMP) is Lidocaine (HY-B0185) produced by using GMP guidelines. GMP small molecules work appropriately as an auxiliary reagent for cell therapy manufacture. Lidocaine 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 (GMP)
  • HY-10529R
    Betulinic acid (Standard)
    		Modulator
    Betulinic acid (Standard) is the analytical standard of Betulinic acid. This product is intended for research and analytical applications. Betulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties.
    Betulinic acid (Standard)
  • HY-W012349
    2′-Hydroxychalcone
    		Inhibitor
    2′-Hydroxychalcone is a hydroxyl derivative of chalcones with anticancer activities. 2'-Hydroxychalcone inhibits NF-κB pathway and induces autophagy and apoptosis in breast cancer cells. 2′-Hydroxychalcone shows a better antifungal activity against the complex Paracoccidioides spp.
    2′-Hydroxychalcone
  • HY-B0898R
    Ceftiofur sodium (Standard)
    		Inhibitor
    Ceftiofur sodium (Standard) is the analytical standard of Ceftiofur sodium (HY-B0898). This product is intended for research and analytical applications. 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 (Standard)
  • HY-153516
    NIK-IN-2
    		Inhibitor
    NIK-IN-2 (compound 1) is a potent inhibitor of NF-κB-inducing kinase (NIK), with the pIC50 of 7.4. NIK-IN-2 plays an important role in cancer research.
    NIK-IN-2
  • HY-N0474R
    Tyrosol (Standard)
    		Inhibitor
    Tyrosol (Standard) is the analytical standard of Tyrosol. This product is intended for research and analytical applications. 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 (Standard)
  • HY-152169
    BIHC
    		Inhibitor ≥98.0%
    BIHC is a TNF blocker with anti-inflammatory activity. BIHC can significantly inhibit the proliferation of hepatocellular carcinoma (HCC) cells and exhibits potent cytotoxicity against the HepG2 cell line, capable of inducing cell apoptosis , while demonstrating relatively low toxicity towards normal hepatocytes. Additionally, BIHC can be used for research on inflammatory bowel disease (IBD).
    BIHC
  • HY-B0190B
    Nafamostat hydrochloride
    Nafamostat hydrochloride, an anticoagulant, is a synthetic serine protease inhibitor. Nafamostat hydrochloride has anticancer and antivirus effect. Nafamostat hydrochloride induces apoptosis by up-regulating the expression of tumor necrosis factor receptor-1 (TNFR1). Nafamostat hydrochloride can be used in the development of the pathological thickening of the arterial wall.
    Nafamostat hydrochloride
  • HY-118828B
    12-Oxo phytodienoic acid (≥90%)
    		Inhibitor
    12-Oxo phytodienoic acid (≥90%) (12-OPDA (≥90%)) is a plant lipid-derived anti-inflammatory compound. 12-Oxo phytodienoic acid (≥90%) suppresses neuroinflammation by inhibiting Nf-κB and p38 MAPK signaling in Lipopolysaccharides (LPS) (HY-D1056)-activated cells. 12-Oxo phytodienoic acid (≥90%) can be used for neurodegenerative diseases research.
    12-Oxo phytodienoic acid (≥90%)
  • HY-19498
    WAY-204688
    		Inhibitor 99.89%
    WAY-204688 is an estrogen receptor (ER-α) selective, orally active inhibitor of NF-κB transcriptional activity with an IC50 of 122 ± 30 nM for NF-κB-luciferase (NF-κB-luc) in HAECT-1 cells.
    WAY-204688
  • HY-N8707
    Homobutein
    		Inhibitor 98.35%
    Homobutein a natural chalcones (can be found in many medicinal plants, fruits, vegetables, spices and nuts), is a potent HDACs/NF-κB dual inhibitor with IC50s of 190 and 38 μM, respectively. Homobutein also a chelator of iron (II and III) cations, shows various activities, including anticancer, anti-inflammatory, antiparasite and antioxidation.
    Homobutein
  • HY-101410R
    SDMA (Standard)
    		Activator
    SDMA (Standard) is the analytical standard of SDMA. This product is intended for research and analytical applications. SDMA (Symmetric dimethylarginine) is an endogenous inhibitor of nitric oxide (NO) synthase activity. SDMA, a novel kidney biomarker, permits earlier diagnosis of kidney disease than traditional creatinine testing.
    SDMA (Standard)
  • HY-B1619S
    Cromolyn-d5
    		Inhibitor
    Cromolyn-d5 (Cromoglycate-d5) is the deuterium labeled Cromolyn (HY-B1619). Cromolyn (Cromoglycate) is an orally active GSK-3β inhibitor with an IC50 of 2.0 μM. Cromolyn is also a mast cell stabilizer that can inhibit the release of mediators from mast cells, regulate reflex bronchoconstriction, and reduce non-specific bronchial hyperreactivity, and Cromolyn can be used in the research of bronchial asthma. In addition, Cromolyn has multiple activities such as anti-inflammatory, anti-allergic, anti-histamine, anti-cancer, and neuroprotective effects.
    Cromolyn-d<sub>5</sub>
  • HY-117726
    WAY-169916
    		Inhibitor 99.60%
    WAY-169916 is a pathway-selective ligand of ER (estrogen receptor) that acts by inhibiting NF-kB transcriptional activity. WAY-169916 has potent anti-inflammatory effect.
    WAY-169916
  • HY-N2908R
    Atraric acid (Standard)
    		Inhibitor
    Atraric acid (Standard) is the analytical standard of Atraric acid. This product is intended for research and analytical applications. Atraric acid (Methyl atrarate) is a specific androgen receptor (AR) antagonist with anti-inflammatory and anticancer effects. Atraric acid represses the expression of the endogenous prostate specific antigen gene in both LNCaP and C4-2 cells. Atraric acid can also inhibit the synthesis of NO and cytokine, and suppress the MAPK-NFκB signaling pathway. Atraric acid can be used to research prostate diseases and inflammatory diseases[1][2].
    Atraric acid (Standard)
  • HY-135317B
    Emavusertib hydrochloride
    		Inhibitor
    Emavusertib hydrochloride (CA-4948 tosylate) is the hydrochloride salt form of Emavusertib (HY-135317). Emavusertib hydrochloride is an orally active inhibitor for IRAK4 (IC50=57 nM) and FLT3. Emavusertib hydrochloride inhibits NF-κB and MyD88 signaling pathways, reduces the generation of pro-inflammatory cytokines like IL-6 and IL-10, thereby exhibiting anti-inflammatory and anti-proliferative activities against cancer cells, leading to cell apoptosis. Emavusertib hydrochloride exhibits antitumor activity in mouse model.
    Emavusertib hydrochloride
  • HY-N0168AS
    (Rac)-Hesperetin-d3
    (Rac)-Hesperetin-d3 is the deuterium labeled (Rac)-Hesperetin. (Rac)-Hesperetin is the racemate of Hesperetin. Hesperetin is a natural flavanone, and acts as a potent and broad-spectrum inhibitor against human UGT activity. Hesperetin induces apoptosis via p38 MAPK activation.
    (Rac)-Hesperetin-d<sub>3</sub>
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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