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-B1135R
    Benzbromarone (Standard)
    Benzbromarone (Standard) is the analytical standard of Benzbromarone. This product is intended for research and analytical applications. Benzbromarone is an orally active anti-gout agent. Benzbromarone has anti-infammatory, anti-oxidative stress and nephroprotective effects. Benzbromarone can be used for the research of hyperuricemia and gout.
    Benzbromarone (Standard)
  • 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-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-N0168AS1
    (Rac)-Hesperetin-13C,d3
    Inhibitor 99.3%
    (Rac)-Hesperetin-13C,d3 is the 13C- and deuterium labeled (Rac)-Hesperetin. (Rac)-Hesperetin is the racemate of Hesperetin (HY-N0168), an orally active multi-target inhibitor. (Rac)-Hesperetin exhibits significant anti-tumor and anti-inflammatory activities by blocking the TGF-β1-mediated Fyn/RhoA signaling axis and the TLR4-MyD88-NF-κB inflammatory pathway. (Rac)-Hesperetin inhibits the formation of actin stress fibers and the migration and invasion of cancer cells, and is suitable for triple-negative breast cancer research. In inflammation models, (Rac)-Hesperetin effectively alleviates lung injury by reducing the release of pro-inflammatory mediators and regulating the activity of oxidative stress enzymes, and is suitable for acute lung injury research. (Rac)-Hesperetin also interferes with the entry and early replication processes of channel catfish virus, inhibits viral gene expression and progeny virus production, thereby protecting cells from virus-induced cytopathic effects.
    (Rac)-Hesperetin-<sup>13</sup>C,d<sub>3</sub>
  • HY-19918A
    Anatabine dicitrate
    Inhibitor 99.03%
    Anatabine dicitrate is a tobacco alkaloid that can cross the blood-brain barrier. Anatabine dicitrate is a potent α4β2 nAChR agonist. Anatabine dicitrate inhibits NF-κB activation lower amyloid-β (Aβ) production by preventing the β-cleavage of amyloid precursor protein (APP). Anatabine dicitrate has anti-inflammatory effects and has the potential for neurodegenerative disorders treatment.
    Anatabine dicitrate
  • HY-B0190
    Nafamostat
    Nafamostat, an anticoagulant, is a synthetic serine protease inhibitor. Nafamostat has anticancer and antivirus effect. Nafamostat induce apoptosis by up-regulating the expression of tumor necrosis factor receptor-1 (TNFR1). Nafamostat can be used in the development of the pathological thickening of the arterial wall.
    Nafamostat
  • HY-128853S
    Taurodeoxycholate-d6 sodium
    Inhibitor 99.4%
    Taurodeoxycholate-d6 sodium salt is a bile salt-related anionic detergent. Taurodeoxycholate-d6 sodium salt is formed in the liver by conjugation of deoxycholate with Taurine (HY-B0351). Taurodeoxycholate-d6 sodium salt is used for isolation of membrane proteins including inner mitochondrial membrane proteins. Taurodeoxycholate-d6 (TDCA) exhibits anti-inflammatory and neuroprotective effects.
    Taurodeoxycholate-d<sub>6</sub> sodium
  • HY-135702
    UBS109
    Inhibitor 99.20%
    UBS109, as a curcumin analogue, can promote the differentiation and mineralization of osteoblasts. UBS109 shows to regulate bone cell function by activating Smad and inhibiting NF-kB. UBS109 can be used in bone tissue engineering and osteoporosis research.
    UBS109
  • HY-N0256R
    Hederagenin (Standard)
    Inhibitor
    Hederagenin (Standard) is the analytical standard of Hederagenin. This product is intended for research and analytical applications. Hederagenin is a triterpenoid saponin with orally active and antitumor activity. Hederagenin can inhibit the expression of iNOS, COX-2, and NF-κB in cells induced by LPS stimulation. Hederagenin also increases ROS production in cancer cells, disrupts mitochondrial membrane potential, and induces apoptosis. Hederagenin also sensitizes cancer cells to Cisplatin (HY-17394) and Paclitaxel (HY-B0015), enhancing induced apoptosis. Hederagenin also has preventive potential against alcoholic liver injury.
    Hederagenin (Standard)
  • HY-124958
    NDMC101
    Inhibitor 99.91%
    NDMC101 is a potent osteoclastogenesis inhibitor and inhibits osteoclast differentiation via down-regulation of NFATc1-modulated gene expression. NDMC101 is similar to the DPP4 substrate and is a significant inhibitor of early T-cell activation via DPP4 inhibition. NDMC101can be used for study of bone disorders, such as rheumatoid arthritis, and synovial inflammation et al.
    NDMC101
  • HY-W015883S1
    Fumaric acid-13C2
    99.9%
    Fumaric acid-13C2 is the 13C-labeled Fumaric acid (HY-W015883). Fumaric acid is an unsaturated dicarbonic acid, an intermediate product of the citric acid cycle that provides intracellular energy in the form of ATP. Fumaric acid exerts anti-inflammatory effects by inhibiting the NF-κB signaling pathway dependent on p38 MAPK. Fumaric acid can be used in the study of pregnancy-induced hypertension.
    Fumaric acid-<sup>13</sup>C<sub>2</sub>
  • HY-N0587R
    Demethylzeylasteral (Standard)
    Inhibitor
    Demethylzeylasteral (Standard) is the analytical standard of Demethylzeylasteral. This product is intended for research and analytical applications. Demethylzeylasteral is an orally active triterpenoid compound isolated from Tripterygium wilfordii, which has functions such as anti-inflammatory, anti-tumor, anti fertility, estrogen metabolism regulation, immune suppression, and immune system regulation .
    Demethylzeylasteral (Standard)
  • HY-N2585
    Isodeoxyelephantopin
    Inhibitor 98.04%
    Isodeoxyelephantopin is a sesquiterpene lactone isolated from Elephantopus scaber. Isodeoxyelephantopin induces ROS generation, suppresses NF-κB activation. Isodeoxyelephantopin also modulates LncRNA expression and exhibit activities against breast cancer.
    Isodeoxyelephantopin
  • HY-P10897
    SjDX5-271
    Inhibitor 98.90%
    SjDX5-271 is a small 3 kDa peptide. SjDX5-271 inhibits the TLR4/MyD88/NF-κB signaling pathway. SjDX5-271 induces cell polarization. SjDX5-271 alleviats hepatic inflammation. SjDX5-271 protects mice against liver ischemia-reperfusion injury.
    SjDX5-271
  • HY-14811
    Beloranib
    Modulator
    Beloranib (ZGN-440; CKD-732 free base) is a selective, irreversible inhibitor of methionine aminopeptidase MetAP2 that suppresses appetite and increases energy expenditure. Beloranib blocks the enzymatic cleavage of N-terminal methionine from nascent proteins by forming a covalent bond with MetAP2, thereby regulating fatty acid metabolism, adrenergic signaling, and hypothalamic NF-κB expression. Beloranib significantly reduces food intake, body weight, and fat accumulation, while improving glucose tolerance, insulin sensitivity, and lipid metabolism. Beloranib also elevates energy expenditure and fat oxidation levels, without affecting body temperature, spontaneous activity, or the inflammatory cytokine IL-1β. Beloranib can be used in research on obesity and hypothalamic obesity.
    Beloranib
  • HY-N11768
    4-Methoxylonchocarpin
    Inhibitor 98.0%
    4-Methoxylonchocarpin is an orally active anti-inflammatory agent. 4-methoxylonchocarpin inhibits the binding of LPS to Toll-like Receptor (TLR) TLR4 to inhibit NF-κB activation and TNF Receptor and IL-6 expression. 4-Methoxylonchocarpin also inhibits the phosphorylation of TGF-beta activated kinase 1 and TNBS-induced expression of IL-1β, IL-17A, and TNF. 4-methoxylonchocarpin can improve 2,4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model.
    4-Methoxylonchocarpin
  • HY-N11722
    Panduratin A
    Inhibitor 99.9%
    Panduratin A is an orally active natural compound with multiple pharmacological activities. By specifically inhibiting the NF-κB signaling pathway, Panduratin A exerts potent anti-inflammatory and antioxidant effects in intestinal and vascular inflammation models. Panduratin A exerts a definite protective effect against Colistin (HY-113678)-induced nephrotoxicity by alleviating oxidative stress, improving mitochondrial dysfunction and inhibiting cell apoptosis. Panduratin A activates autophagy via an AMPK-dependent pathway and exhibits anti-tuberculosis activity. Panduratin A exerts antiviral effects by inhibiting the methyltransferase (DNA Methyltransferase) of SARS-CoV-2.
    Panduratin A
  • HY-121309
    Doxorubicinone
    Inhibitor 98.29%
    Doxorubicinone (Adriamycin aglycone) is the aglycone of the antibiotic Doxorubicin (HY-15142A), i.e., its sugar-free parent nucleus structure. Doxorubicinone does not induce DNA damage or bind to RelA, but still downregulates the expression of pro-inflammatory cytokines (such as TNF, IL-12, etc.) regulated by the NF-κB pathway. Doxorubicinone can be used in sepsis-related research.
    Doxorubicinone
  • HY-106029
    4α-TPA
    Control 99.0%
    4α-TPA is an inactive form of TPA, and is used as a negative control for TPA-activated events.
    4α-TPA
  • HY-179421
    PROTAC HDAC6 degrader 7
    Inhibitor
    PROTAC HDAC6 degrader 7 is an orally active, highly efficient, and selective PROTAC degrader targeting histone deacetylase 6 (HDAC6) (IC50 = 118 nM). PROTAC HDAC6 degrader 7 can eliminate both the catalytic and zinc-finger ubiquitin-binding domain. PROTAC HDAC6 degrader 7 inhibits NLRP3 inflammasome assembly and activation, as well as blocks NF-κB signaling, thereby reducing the transcription and release of key inflammatory factors. PROTAC HDAC6 degrader 7 can reduce the mRNA levels of NLRP3, pro-IL-1β, TNF-α, and IL-6. PROTAC HDAC6 degrader 7 can be used for the study of inflammatory bowel disease (IBD).
    PROTAC HDAC6 degrader 7
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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