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-N0168AR
    (Rac)-Hesperetin (Standard)
    Inhibitor
    (Rac)-Hesperetin (Standard) is the analytical standard of (Rac)-Hesperetin. This product is intended for research and analytical applications. (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 (Standard)
  • HY-N0119R
    Naringin Dihydrochalcone (Standard)
    Inhibitor
    Naringin Dihydrochalcone (Standard) is the analytical standard of Naringin Dihydrochalcone. This product is intended for research and analytical applications. Naringin Dihydrochalcone is an artificial sweetener derived from naringin. Naringin is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. Naringin exhibits biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. Naringin suppresses NF-κB signaling pathway.
    Naringin Dihydrochalcone (Standard)
  • HY-N17317
    Isostrictiniin
    Inhibitor
    Isostrictiniin (ITN) is a polyphenolic compound isolated from Nymphaea candida. It upregulates the expression of Nrf2 and HO-1, while downregulating the expression of Keap1. Isostrictiniin reduces the phosphorylation levels of JNK, ERK1/2, p38, IκBα, and NF-κB p65. Isostrictiniin decreases the levels of pro-inflammatory mediators (IL-1β, IL-6, TNF-α, PGE2). Isostrictiniin alleviates LPS-induced acute lung injury and exerts protective effects against acute alcoholic liver injury. Additionally, isostrictiniin exhibits anti-inflammatory, antioxidant, and anti-fibrotic activities.
    Isostrictiniin
  • HY-N2434R
    [10]-Shogaol (Standard)
    Inhibitor
    -Shogaol (Standard) is the analytical standard of -Shogaol (HY-N2434). This product is intended for research and analytical applications. [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 (Standard)
  • HY-N1489
    14-Deoxy-11,12-didehydroandrographiside
    Inhibitor
    14-Deoxy-11,12-didehydroandrographiside is a compound isolated from A. paniculate.
    14-Deoxy-11,12-didehydroandrographiside
  • HY-P11296
    LLVK
    Inhibitor
    LLVK is a selective IκB phosphorylation inhibitor. LLVK reduces LPS-induced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). LLVK is promising for research of inflammatory bowel disease and rheumatoid arthritis.
    LLVK
  • HY-15122AR
    Sinomenine hydrochloride (Standard)
    Inhibitor
    Sinomenine hydrochloride (Standard) is the analytical standard of Sinomenine hydrochloride. This product is intended for research and analytical applications. Sinomenine hydrochloride (Cucoline hydrochloride), an alkaloid extracted from Sinomenium acutum, is a blocker of the NF-κB activation. Sinomenine also is an activator of μ-opioid receptor.
    Sinomenine hydrochloride (Standard)
  • HY-N0250R
    Saikosaponin D (Standard)
    Inhibitor
    Saikosaponin D (Standard) is the analytical standard of Saikosaponin D. This product is intended for research and analytical applications. Saikosaponin D is a triterpene saponin isolated from Bupleurum, with anti-inflammatory, anti-bacterial, anti-tumor, and anti-allergic activities; Saikosaponin D inhibits selectin, STAT3 and NF-kB and activates estrogen receptor-β.
    Saikosaponin D (Standard)
  • HY-N0602R
    Ginsenoside Rg2 (Standard)
    Inhibitor
    Ginsenoside Rg2 (Standard) is the analytical standard of Ginsenoside Rg2. This product is intended for research and analytical applications. Ginsenoside Rg2 is one of the major active components of ginseng. Ginsenoside Rg2 inhibits VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS). Ginsenoside Rg2 also reduces 1-42 accumulation.
    Ginsenoside Rg2 (Standard)
  • HY-163829
    TLR2 agonist 1
    Agonist
    TLR2 agonist 1 (Compound R-7d) is an agonist for human toll-like receptor 2 (TLR 2) with an EC50 of 116 pM. TLR2 agonist 1 enhances NF-κB promoter activation through TLR2/TLR1 heterodimers.
    TLR2 agonist 1
  • HY-N10768
    1-Dehydro-[10]-gingerdione
    Inhibitor
    1-Dehydro-[10]-gingerdione directly inhibits IKKβ activity by targeting the activation loop of IKKβ, thus disrupting IKKβ-catalysed IκBα phosphorylation in macrophages stimulated with agonists. 1-Dehydro-[10]-gingerdione inhibits LPS (HY-D1056)-induced NF-κB transcriptional activity. 1-Dehydro-[10]-gingerdione has the potential for NF-κB-associated inflammation and autoimmune disorders research.
    1-Dehydro-[10]-gingerdione
  • HY-161266
    COX-2/NLRP3-IN-1
    Inhibitor
    COX-2/NLRP3-IN-1 (Compound 6k) is a COX-2/NLRP3 inhibitor with a IC50 of 1.53 μM for COX-2. COX-2/NLRP3-IN-1 exerts anti-inflammatory effects by inhibiting the NF-κB/NLRP3 signaling pathway.
    COX-2/NLRP3-IN-1
  • HY-W012732S2
    Isoquinoline-15N
    Isoquinoline-15N is the 15N-labeled Isoquinoline (HY-W012732). Isoquinoline is an analog of pyridine. Isoquinoline-based alkaloids, such as p-tolyl bisisoquinoline, phthaloyl isoquinoline, and naphthyl isoquinoline, exhibit anticancer activity. Berberine, an isoquinoline alkaloid, exerts anti-inflammatory effects in diabetic mice by downregulating the gene expression ratios of pro-/anti-inflammatory and Th1/Th2 cytokines. Additionally, some isoquinoline-based compounds also possess antidepressant, antibacterial, antimalarial, and anti-HIV activities.
    Isoquinoline-<sup>15</sup>N
  • HY-N6246R
    Asperulosidic Acid (Standard)
    Inhibitor
    Asperulosidic Acid (Standard) is the analytical standard of Asperulosidic Acid. This product is intended for research and analytical applications. Asperulosidic Acid (ASPA), a bioactive iridoid glycoside, is extracted from the herbs of Hedyotis diffusa Willd. Asperulosidic Acid (ASPA) has anti-tumor, anti-oxidant, and anti-inflammatory activities. ASPA is related to the inhibition of inflammatory cytokines (TNF-α, IL-6) and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways.
    Asperulosidic Acid (Standard)
  • HY-149087
    MR2938
    Inhibitor
    MR2938 is a potent AChE inhibitor, with an IC50 of 5.04 μM. MR2938 also suppresses NO production obviously (IC50 = 3.29 μM). MR2938 suppresses the neuroinflammation through blocking MAPK/JNK and NF-κB signaling pathways. MR2938 can be used for Alzheimer’s disease (AD) research.
    MR2938
  • HY-10071A
    Y-27632 hydrochloride hydrate
    Inhibitor 99.65%
    Y-27632 hydrochloride hydrate is a ROCK inhibitor with Ki values of 220 nM and 300 nM for ROCK1 and ROCK2, respectively. Y-27632 hydrochloride hydrate exerts anti-inflammatory and immunomodulatory effects in systemic lupus erythematosus models by inhibiting the ROCK/NF-κB pathway. Y-27632 hydrochloride hydrate enhances autophagy by inhibiting the AKT/mTOR pathway, thereby inducing apoptosis apoptosis in oral squamous cell carcinoma. Y-27632 hydrochloride hydrate induces the formation of tunneling nanotubes in ARPE-19 cells and significantly enhances mitochondrial transfer through these channels. Y-27632 hydrochloride hydrate promotes neurite outgrowth in PC12 cells by activating the Rac1/NOX1/ROS/AKT/PAK1 signaling cascade.
    Y-27632 hydrochloride hydrate
  • HY-182053
    Antiproliferative agent-76
    Inhibitor
    Antiproliferative agent-76 (Compound II-2) is an 8-sulfonamidoquinoline derivative and a selective anticancer agent. Antiproliferative agent-76 blocks the NF-κB and WNT signaling pathways. Antiproliferative agent-76 promotes cancer cell Apoptosis. Antiproliferative agent-76 exhibits anticancer activity against colorectal cancer and leukemia.
    Antiproliferative agent-76
  • HY-168482
    NF-κB/MAPK-IN-2
    Inhibitor
    NF-κB/MAPK-IN-2 (compound 14) is a potent NF-κB and MAPK Inhibitor. NF-κB/MAPK-IN-2 decreases the protein expression of p-p65, p-IκB, p-p38, p-JNK, and p-ERK. NF-κB/MAPK-IN-2 reduces the LPS-induced release of TNF-α and IL-6. NF-κB/MAPK-IN-2 inhibits nuclear translocation of p65 and c-Fos. NF-κB/MAPK-IN-2 has the potential for the research of sepsis.
    NF-κB/MAPK-IN-2
  • HY-N17131
    24-O-Acetyllycoclavanol
    Inhibitor
    24-O-Acetyllycoclavanol (compound 1) is a triterpenoid anti-inflammatory agent that selectively targets the NF-κB and ERK1/2 signaling pathways. It exerts its anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and COX-2 expression, reducing the production of inflammatory mediators such as nitric oxide (NO), IL-1β, and IL-8. 24-O-Acetyllycoclavanol can be used in research related to inflammatory bowel disease (IBD). 24-O-Acetyllycoclavanol can be biologically isolated from the ethyl acetate extract of Lycopodium clavatum.
    24-O-Acetyllycoclavanol
  • HY-N0803S
    Myrcene-d6
    Inhibitor
    Myrcene-d6 is the deuterium labeled Myrcene. Myrcene (β-Myrcene) is a type of aromatic compound that inhibits TNFα and NF-κB activity. Myrcene has anti-invasive action, inhibits cell cycle, and leads to cancer cell apoptosis. Myrcene has strong blood protection effect, anti-inflammation, and anti-inflammatory activity.
    Myrcene-d<sub>6</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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