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-N0738
    Stachydrine hydrochloride
    Inhibitor 99.90%
    Stachydrine hydrochloride is the major active constituent of Leonurus artemisia, which is a potential therapy for cardiovascular diseases. Stachydrine can inhibit the NF-κB signal pathway. Anti-hypertrophic activities.
    Stachydrine hydrochloride
  • HY-160141
    Catadegbrutinib
    Inhibitor 99.18%
    BGB-16673 (BGB-16673) is an orally active, selective BTK PROTAC degrader (IC50=0.69 nM). BGB-16673 ligates BTK to E3 ubiquitin ligase, causing BTK to undergo polyubiquitination, which is then recognized and degraded by the proteasome, thereby exerting efficient BTK degradation activity. BGB-16673 can be used in the research of B-cell malignancies such as chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma.
    Catadegbrutinib
  • HY-N0217
    Benzoylaconine
    Inhibitor 99.92%
    Benzoylaconine (Benzoylaconitine) is an orally active monoester alkaloid found in the traditional Chinese medicine Aconitum carmichaelii. Benzoylaconine is an ACE2 agonist (EC50: 1.5 μM) with antihypertensive and anti-heart failure effects. Benzoylaconine inhibits TLR-induced MAPK and NF-κB pathways to exert anti-inflammatory effects. Benzoylaconine upregulates the protein levels of P-gp, MRP2, and has anti-tumor effects.
    Benzoylaconine
  • HY-N0815
    Resibufogenin
    Inhibitor 99.93%
    Resibufogenin is an orally active anticancer agent. Resibufogenin can be extracted from toad venom. Resibufogenin blocks signaling pathways such as PI3K/Akt, NF-κB, AP-1, activates GSK-3β, and regulates cyclin D1. Resibufogenin can activate central neurons. Resibufogenin has anti-inflammatory activity. Resibufogenin has anti-tumor effects on a variety of tumors such as multiple myeloma, renal cancer, colorectal cancer, pancreatic cancer, and glioma.
    Resibufogenin
  • HY-N0279
    Cardamonin
    Inhibitor 99.80%
    Cardamonin can be found from cardamom, and can target various signaling molecules, transcriptional factors, cytokines and enzymes. Cardamonin can inhibit mTOR, NF-κB, Akt, STAT3, Wnt/β-catenin and COX-2. Cardamonin shows anticancer, anti-inflammatory, antimicrobial and antidiabetic activities.
    Cardamonin
  • HY-N0563
    Alizarin
    Inhibitor 99.48%
    Alizarin is a natural dye. Alizarin can be extracted from the roots of madder plant. Alizarin activates AMPK and VEGFR2/eNOS pathway. Alizarin regulates PI3K/Akt and inhibits NF-κB pathway. Alizarin enhances CYP1A1 enzyme activity. Alizarin has protective effects on hypertension and vascular endothelial dysfunction. Alizarin has anti-tumor activity against multiple cancers including pancreatic cancer, breast cancer, osteosarcoma and liver cancer. Alizarin has been widely used as a pigment in textile fabrics and paintings.
    Alizarin
  • HY-D0939
    Direct Blue 1
    Inhibitor
    Direct Blue 1 (Chicago Sky Blue 6B) is a complex dye for background autofluorescence in immunofluorescence histochemistry. Direct Blue 1 is a potent and competitive VGLUT inhibitor. Direct Blue 1 can inhibit the Aβ-binding small molecule PrP ligand. Direct Blue 1 has anti-inflammatory activity.
    Direct Blue 1
  • HY-N0220
    Dauricine
    Inhibitor 99.75%
    Dauricine, a bisbenzylisoquinoline alkaloid in Menispermum dauricum, possesses anti-inflammatory activity. Dauricine inhibits cell proliferation and invasion, and induces apoptosis by suppressing NF-κB activation in a dose- and time-dependent manner in colon cancer.
    Dauricine
  • HY-121389
    Hexadecanamide
    Inhibitor 99.64%
    Hexadecanamide (Palmitamide) is a fatty acid amide that has orally active anti-allergic, antioxidant, and neuroprotective effects. Hexadecanamide exerts protective effects in Staphylococcus aureus- and SARA-induced mastitis. Hexadecanamide suppresses S. aureus-induced activation of the NF-κB pathway and improves blood-milk barrier integrity. Hexadecanamide activates PPARα. Hexadecanamide enhances sperm motility in vitro. Hexadecanamide can be studied in research for mastitis and asthenozoospermia.
    Hexadecanamide
  • HY-130603
    DCZ0415
    Inhibitor 99.81%
    DCZ0415, a potent TRIP13 inhibitor, impairs nonhomologous end joining repair and inhibits NF-κB activity. DCZ0415 induces anti-myeloma activity in vitro, in vivo, and in primary cells derived from drug-resistant myeloma patients.
    DCZ0415
  • HY-17403
    Manidipine dihydrochloride
    Inhibitor 99.84%
    Manidipine dihydrochloride is a third-generation, lipophilic, orally active and highly vasoselective calcium channel antagonist (IC50 = 2.6 nM in guinea-pig ventricular cells) and acts as an antihypertensive agent. Manidipine effectively reduces blood pressure as well as improving insulin sensitivity, renal protection, and antiatherosclerotic activity. Manidipine also exerts anti-inflammatory activity mediated by NF-κB and antiviral activity against many flavivirus and negative-strand RNA viruses through the inhibition of calcium channel. Manidipine is widely applied to research of cardiovascular, metabolic disease and infection.
    Manidipine dihydrochloride
  • HY-N6727
    Gliotoxin
    Inhibitor 99.51%
    Gliotoxin is a secondary metabolite, the most abundant mycotoxin secreted by A. fumigatus, inhibits the phagocytosis of macrophages and the immune functions of other immune cells . Gliotoxin inhibits inducible NF-κB activity by preventing IκB degradation, which consequently induces host-cell apoptosis. Gliotoxin activates PKA and increases intracellular cAMP concentration; modulates actin cytoskeleton rearrangement to facilitate A. fumigatus internalization into lung epithelial cells. Gliotoxin is a potent NOTCH2 transactivation inhibitor, can effectively induce apoptosis of chronic lymphocytic leukemia (CLL) cells.
    Gliotoxin
  • HY-126741
    Azadirachtin
    Inhibitor 99.06%
    Azadirachtin is an oral active triterpenoid compound with anticancer, antimalarial, anti-inflammatory, and insecticidal activities. Azadirachtin induces cell apoptosis through the mitochondrial pathway (by inhibiting Bcl-2/Bax ratio or activating Apaf-1 and caspase-3) or through death receptors (by inhibiting TNFR activation). Additionally, Azadirachtin exerts its anti-inflammatory effects by inhibiting NF-кB signaling pathway activation, and it exhibits insecticidal activity by inducing apoptosis in insect cells.
    Azadirachtin
  • HY-N0390S9
    L-Glutamine-15N-1
    Inhibitor 98.0%
    L-Glutamine-15N-1 is the 15N-labeled L-Glutamine (HY-N0390). L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na+-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.
    L-Glutamine-<sup>15</sup>N-1
  • HY-N0591
    Dehydrocostus Lactone
    Inhibitor 99.98%
    Dehydrocostus Lactone ((-)-Dehydrocostus lactone) is a natural sesquiterpene that can be isolated from Saussurea lappa. Dehydrocostus Lactone has multiple activities such as anti-inflammatory, antibacterial, anti-tumor, and immunomodulatory effects. Dehydrocostus Lactone has an MIC of 2 µg/mL against Mycobacterium tuberculosis. Dehydrocostus Lactone can also inhibit the killing activity of cytotoxic T lymphocytes and induce apoptosis in tumor cells.
    Dehydrocostus Lactone
  • HY-N0043
    Ginsenoside Rd
    Inhibitor 99.88%
    Ginsenoside Rd inhibits TNFα-induced NF-κB transcriptional activity with an IC50 of 12.05±0.82 μM in HepG2 cells. Ginsenoside Rd inhibits expression of COX-2 and iNOS mRNA. Ginsenoside Rd also inhibits Ca2+ influx. Ginsenoside Rd inhibits CYP2D6, CYP1A2, CYP3A4, and CYP2C9, with IC50s of 58.0±4.5 μM, 78.4±5.3 μM, 81.7±2.6 μM, and 85.1±9.1 μM, respectively.
    Ginsenoside Rd
  • HY-N0103
    Sophocarpine
    Inhibitor 99.85%
    Sophocarpine is a PTEN activator and an inhibitor of PI3K/Akt, MEK/ERK, and NF-κB signaling pathways. Sophocarpine upregulates PTEN expression and inhibits PI3K/Akt phosphorylation, arrests tumor cell cycle and induces apoptosis. Sophocarpine inhibits MEK/ERK phosphorylation and VEGF secretion, reducing tumor cell migration. Sophocarpine can also inhibit NF-κB activation and p38 and JNK phosphorylation, reduce the expression of inflammatory factors such as iNOS and COX-2, and activate the Nrf2/HO-1 pathway to reduce oxidative stress. Sophocarpine has anti-tumor, anti-inflammatory, antioxidant and anti-apoptotic effects, and can be used in the research of cancers such as glioblastoma and colorectal cancer, inflammation-related diseases, and Doxorubicin (HY-15142A)-induced cardiac damage.
    Sophocarpine
  • HY-N1380
    Guaiacol
    Inhibitor 99.96%
    Guaiacol, a phenolic compound, inhibits LPS-stimulated COX-2 expression and NF-κB activation. Anti-inflammatory activity.
    Guaiacol
  • HY-10454
    Delanzomib
    Inhibitor 98.0%
    Delanzomib (CEP-18770) is a potent and orally active chymotrypsin-like activity of the proteasome inhibitor with an IC50 of 3.8 nM. Delanzomib inhibits NF-κB activity, induces cancer cell apoptotic, and has strong antiangiogenic and anti-cancer activities.
    Delanzomib
  • HY-N0806
    Sweroside
    Inhibitor 99.76%
    Sweroside is an iridoid glycoside that targets multiple targets, including the Keap1/Nrf2 axis, NLRP3 inflammasome, SIRT1, NF-κB, AMPK/mTOR pathway, and caspase family. Sweroside promotes Nrf2 nuclear translocation by competitively binding to Keap1. Sweroside also inhibits oxidative stress and NLRP3-mediated pyroptosis by activating Nrf2, inhibits NF-κB inflammatory pathway by activating SIRT1, and promotes autophagy and induces caspase-dependent apoptosis via the AMPK/mTOR pathway. Sweroside has antioxidant, anti-inflammatory, anti-apoptotic, and lipid metabolism regulating activities, and can be used in the research of myocardial ischemia-reperfusion injury, leukemia, acute lung injury, non-alcoholic fatty liver disease, and other fields.
    Sweroside
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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