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-10704
    PTP1B-IN-1
    Inhibitor 99.71%
    PTP1B-IN-1 (Compound 7a) is a small molecule inhibitor of PTP1B with an IC50 value of 1.6 mM. It is often used as the mother core for derivatives of analogues.
    PTP1B-IN-1
  • HY-130237
    Cinnamtannin B-1
    Inhibitor 99.16%
    Cinnamtannin B-1 is a anthocyanidin. Cinnamtannin B-1 inhibits the osteoclast formation by inhibiting NF-kB signaling pathway and ROS generation. Cinnamtannin B-1 exhibits antioxidant, anti-inflammatory, antitumor and anti-platelet aggregation activities. Cinnamtannin B-1 is orally active.
    Cinnamtannin B-1
  • HY-116626
    SM-7368
    Inhibitor 99.77%
    SM-7368 is a potent NF-kB inhibitor that targets downstream of MAPK p38 activation. SM-7368 inhibits TNF-α-induced MMP-9 upregulation. SM-7368 can be used for the research of chemotherapies targeting TNF-α-mediated tumor invasion and metastasis .
    SM-7368
  • HY-N0906
    Ginsenoside Rk3
    Inhibitor 99.79%
    Ginsenoside Rk3 is present in the roots Panax ginseng herbs. Ginsenoside Rk3 significantly inhibits TNF-α-induced NF-κB transcriptional activity, with an IC50 of 14.24±1.30 μM in HepG2 cells.
    Ginsenoside Rk3
  • HY-N2217
    Rotundic acid
    Inhibitor 99.41%
    Rotundic acid is an orally effective triterpenoid with a Kd value of 51.3 µM for PTP1B. Rotundic acid downregulates the AKT/mTOR pro-survival pathway and modulates the MAPK pathway. Rotundic acid induces cell cycle S-phase arrest, DNA damage and apoptosis; it inhibits migration, invasion, angiogenesis and proliferation of cancer cells. Rotundic acid improves leptin sensitivity, regulates gut microbiota and reduces cellular senescence. Rotundic acid can be used in research related to hepatocellular carcinoma, obesity, aging, acute lung injury and type 2 diabetes.
    Rotundic acid
  • HY-N0237
    Atractyloside A
    Inhibitor 98.11%
    Atractyloside A is an orally active inhibitor of the TLR4/MyD88/NF-κB signaling pathway and also an opener of the mitochondrial permeability transition pore (MPTP). Atractyloside A interferes with the activation of the TLR4/MyD88/NF-κB pathway, thereby inhibiting intestinal inflammatory responses. Atractyloside A reverses mucin synthesis impairment, improves intestinal barrier integrity, and restores homeostasis by altering the composition of the gut microbiota. Atractyloside A can be used in studies related to spleen deficiency diarrhea and myocardial injury.
    Atractyloside A
  • HY-129440
    N-(p-Coumaroyl) Serotonin
    Inhibitor 99.03%
    N-(p-Coumaroyl) Serotonin is an orally active polyphenol found in safflower seeds with potent anti-inflammatory, antioxidant, and antitumor activities. N-(p-Coumaroyl) Serotonin suppresses NF‑κB, TLR4/MyD88 and MAPK signaling, activates NQO1/HO‑1 pathways, and inhibits pro‑inflammatory cytokines, iNOS and COX‑2 and ROS production. N-(p-Coumaroyl) Serotonin induces S‑phase arrest and apoptosis in glioblastoma cells, reduces atherosclerotic lesions, and alleviates renal and vascular injuries. N-(p-Coumaroyl) Serotonin acts as a vasodilator, regulates calcium dynamics. N-(p-Coumaroyl) Serotonin can be used for the research of neurodegenerative diseases, atherosclerosis, glioblastoma, and acute renal failure.
    N-(p-Coumaroyl) Serotonin
  • 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-N7067
    Revaprazan hydrochloride
    Inhibitor 99.98%
    Revaprazan hydrochloride is reversible proton pump inhibitor. Revaprazan hydrochloride can inhibit gastric acid secretion and protect gastric mucosa. Revaprazan hydrochloride can inhibit IkappaB-alpha degradation as well as Akt inactivation, resulting in attenuation of H. pylori-induced COX-2 expression. Revaprazan hydrochloride can be used for the researches of infection and inflammmation, such as H. pylori-infected gastric inflammation and gastric ulcer.
    Revaprazan hydrochloride
  • HY-121632
    Quinoclamine
    Inhibitor 99.55%
    Quinoclamine, a naphthoquinone derivative, is a NF-κB inhibitor. Quinoclamine exhibits anti-cancer activity.
    Quinoclamine
  • HY-110398
    5,6,7-Trimethoxyflavone
    Inhibitor 98.76%
    5,6,7-Trimethoxyflavone is a flavonoid compound that can be isolated from plants Callicarpa japonica. 5,6,7-Trimethoxyflavone exhibits antiviral and anti-inflammatory activities through inhibition of NF-κB/AP-1/STAT signaling pathway.
    5,6,7-Trimethoxyflavone
  • HY-N2099
    Onjisaponin B
    Inhibitor 99.31%
    Onjisaponin B is an orally active natural product derived from Polygala tenuifolia. Onjisaponin B inhibits NF-κB p65. Onjisaponin B enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin. Onjisaponin B reduces β-amyloid (Aβ) production. Onjisaponin B reduces radiation-induced cell apoptosis. Onjisaponin B has anti-oxidant and anti-inflammatory activities. Onjisaponin B can be used for neurological disease and radiation injury study, and its metabolite tenuifolin (TF) can enter the brain through the BBB.
    Onjisaponin B
  • HY-114243
    DpC
    Activator 98.73%
    DpC is a selective, orally active iron chelator with anticancer activity. DpC acts on signaling pathway-related targets such as JNK, NF-κB, and its activity is competitively inhibited by another iron chelator Dp44mT (HY-18973). By chelating intracellular iron and copper ions in tumor cells to form redox-active complexes, DpC induces oxidative stress, activates the JNK, NF-κB pathways and downregulates IκBα, upregulates the expressions of neuroglobin and cytoglobin, activates caspase 3/9 to induce tumor cell apoptosis. It also overcomes P-glycoprotein-mediated multidrug resistance through a lysosome-targeting mechanism, and exhibits broad-spectrum synergistic effects when combined with various chemotherapeutic agents. DpC inhibits tumor metastasis and increases TNF-α levels in the tumor microenvironment to enhance endogenous immune responses. DpC is applicable to the research of various malignancies including neuroblastoma, pancreatic cancer, prostate cancer, lung cancer, and breast cancer.
    DpC
  • HY-13219
    Tepoxalin
    Inhibitor 98.46%
    Tepoxalin is an orally active dual inhibitor of Cyclooxygenase/Lipoxygenase, with IC50 values of 4.6 μM (sheep cyclooxygenase), 2.85 μM (rat cyclooxygenase), 0.15 μM (rat 5-lipoxygenase), and 3.0 μM (h12-lipoxygenase), respectively. Tepoxalin inhibits ROS production and NF-κB activation. Tepoxalin suppresses the production of thromboxane B2, leukotriene B4, prostaglandins and cytokines, and blocks platelet aggregation. Tepoxalin exhibits potent anti-inflammatory activity in rats with adjuvant-induced arthritis. Tepoxalin possesses analgesic activity. Tepoxalin shows no ulcerogenic activity within the anti-inflammatory dose range. Tepoxalin can be used in studies related to adjuvant-induced arthritis, skin inflammation and Alzheimer's disease.
    Tepoxalin
  • HY-N4093
    Astringin
    Inhibitor 99.54%
    Astringin (trans-Astringin) is an orally active natural phenolic stilbene glucoside. Astringin can inhibit the production of oxidative stress, inflammatory factors, etc. Astringin has multiple activities such as anti-oxidation, anti-inflammation, and anti-apoptosis. Astringin is also an inhibitor of ferroptosis. Astringin can be used in the research of diseases such as acute lung injury.
    Astringin
  • HY-N4110
    Friedelin
    Inhibitor 99.0%
    Friedelin is derived from the leaves of Maytenus ilicifolia (Mart). Friedelin is an orally active non-competitive inhibitor of CYP3A4, with IC50 and Ki values of 10.79 μM and 6.16 μM, respectively. Friedelin is also a competitive inhibitor of CYP2E1, with IC50 and Ki values of 22.54 μM and 18.02 μM, respectively. Friedelin can be used in research related to inflammation, neurological diseases, and metabolic disorders.
    Friedelin
  • HY-N2497
    Isoliquiritin apioside
    Inhibitor 99.87%
    Isoliquiritin apioside significantly decreases PMA-induced increases in MMP9 activities and suppresses PMA-induced activation of MAPK and NF-κB. Isoliquiritin apioside auppresseses invasiveness and angiogenesis of cancer cells and endothelial cells.
    Isoliquiritin apioside
  • HY-B0380
    Trimebutine
    Inhibitor 99.42%
    Trimebutine is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine inhibits L-type Ca2+ channels and large-conductance calcium-activated potassium channels (BKCa channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine also targets Toll-like receptors, inhibits Toll-like receptor 2/4/7/8/9 signals, and inhibits LPS-induced IRAK1 activation, as well as ERK1/2, JNK and NF-κB activation, thereby exerting anti-inflammatory effects. Trimebutine also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS).
    Trimebutine
  • HY-N0167
    Gynostemma Extract
    Inhibitor 99.92%
    Gynostemma Extract (Gypenoside IX) is a triterpenoid saponin. Gynostemma Extract can be isolated from Panax notoginseng. Gynostemma Extract reduces NFκB nuclear translocation and transcriptional activity by inhibiting the p38 MAPK/Akt/NFκB signaling pathway. Gynostemma Extract reduces the expression of cytokines (COX-2, IL-6) and the production of NO. Gynostemma Extract has anti-inflammatory activity. Gynostemma Extract can be used in the study of liver injury and neuroinflammation.
    Gynostemma Extract
  • HY-100977
    Dimethoxycurcumin
    Inhibitor 98.48%
    Dimethoxycurcumin is a derivative of curcumin that has anti-inflammatory and antioxidant activities.
    Dimethoxycurcumin
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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