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-N0143
    Phlorizin
    Inhibitor 99.93%
    Phlorizin (Floridzin) is an orally active non-selective sodium-glucose cotransporter (SGLT) inhibitor, with an IC50 of 0.04 μM and a Ki of 39 nM against hSGLT2, and an IC50 of 0.17 μM and a Ki of 0.31 μM against hSGLT1. Phlorizin promotes GLUT4 translocation, inhibits gluconeogenesis and promotes glycogen synthesis by activating the PI3K/Akt/mTOR pathway. Phlorizin reduces DNA damage and apoptosis (apoptosis) by inhibiting the NF-κB inflammatory pathway. Phlorizin induces apoptosis via activating the Caspase pathway by antagonizing the JAK/STAT3 and PCK pathways. Phlorizin also exhibits antibacterial, anti-inflammatory and neuroprotective activities.
    Phlorizin
  • HY-N2526
    Nervonic acid
    Inhibitor 99.90%
    Nervonic acid is a monounsaturated fatty acid with oral activity. Nervonic acid exerts anti-inflammatory activity by inhibiting NF-κB signaling. Nervonic acid can be used in the study of neurodegenerative diseases.
    Nervonic acid
  • HY-N0274
    Caffeic acid phenethyl ester
    Inhibitor 99.85%
    Caffeic acid phenethyl ester is a NF-κB inhibitor.
    Caffeic acid phenethyl ester
  • HY-W011474
    Geranylgeraniol
    Inhibitor 99.54%
    Geranylgeraniol is an orally acitve vitamin K2 sub-type, an intermediate of the mevalonate pathway. Geranylgeraniol targets NF-kB signaling pathway and could alleviate LPS-induced microglial inflammation in animal model.
    Geranylgeraniol
  • HY-N0256
    Hederagenin
    Inhibitor 99.95%
    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 can also bind to SKP2, with KD = 67.9 μM. Hederagenin also has preventive potential against alcoholic liver injury.
    Hederagenin
  • HY-15122
    Sinomenine
    Inhibitor 99.96%
    Sinomenine, an alkaloid extracted from Sinomenium acutum, is a blocker of the NF-κB activation. Sinomenine also is an activator of μ-opioid receptor.
    Sinomenine
  • HY-W042416
    N,N-Dimethylacetamide
    Inhibitor 99.96%
    N,N-Dimethylacetamide (DMAc) is an organic solvent with blood-brain transmissibility and an FDA-approved drug excipient. N, N-dimethylacetamide exerts anti-inflammatory activity by inhibiting the NF-κB signaling pathway. N, N-dimethylacetamide can be used in studies of weight gain caused by a high-fat diet and neuroinflammation in Alzheimer's disease.
    N,N-Dimethylacetamide
  • HY-P9958
    Denosumab
    Inhibitor 99.10%
    Denosumab is a human monoclonal antibody that targets the protein RANKL. Denosumab binds to the receptor activator of nuclear factor kappa-B ligand (RANKL) and prevents its binding to the RANK receptor (KD of 0.003 nM for human RANKL). Denosumab promotes proliferation and spermatogenesis. Denosumab prevents bone resorption through inhibition of the NF-κB pathway. Denosumab can be used in bone-related studies.
    Denosumab
  • HY-128853
    Taurodeoxycholate sodium
    Inhibitor 99.80%
    Taurodeoxycholate sodium salt is a bile salt-related anionic detergent. Taurodeoxycholate sodium salt is formed in the liver by conjugation of deoxycholate with Taurine (HY-B0351). Taurodeoxycholate sodium salt is used for isolation of membrane proteins including inner mitochondrial membrane proteins. Taurodeoxycholate (TDCA) exhibits anti-inflammatory and neuroprotective effects.
    Taurodeoxycholate sodium
  • HY-W050154
    Kojic acid
    Inhibitor 99.99%
    Kojic acid is a substance produced by Aspergillus oryzae that is orally effective and can also be absorbed transdermally. Kojic acid exhibits various biological activities, including anti-aging, anti-nematode, antimicrobial, antioxidant, and anti-inflammatory effects. Kojic acid is a Tyrosinase inhibitor with an Mushroom Tyrosinase IC50 of 182.7 μM. Kojic acid prevents melanin production by capturing copper ions that bind to the tyrosinase active site, thus inhibiting its activation. Kojic acid also suppresses the NF-κB and p21 signaling pathways in human keratinocytes. Kojic acid derivatives have anticancer activity.
    Kojic acid
  • HY-N1913
    Danshensu
    Inhibitor 99.90%
    Danshensu (Dan shen suan A), an orally active phenolic compound, can induce Nrf2/HO-1 activation and inhibition of NF-κB pathway. Danshensu reduces reactive oxygen species (ROS) production, upregulates antioxidant defense mechanism and inhibits intrinsic apoptotic pathway. Danshensu displays a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97 μM. Danshensu has anti-oxidation, anti-apoptosis, anti-lung inflammatory and has the potential for COVID-19, cardiovascular and cerebrovascular diseases research.
    Danshensu
  • HY-N0290
    Mangiferin
    Inhibitor 99.92%
    Mangiferin is a Nrf2 activator. Mangiferin suppresses nuclear translocation of the NF-κB subunits p65 and p50. Mangiferin exhibits antioxidant, antidiabetic, antihyperuricemic, antiviral, anticancer and antiinflammatory activities.
    Mangiferin
  • HY-N0890
    Tubeimoside I
    Inhibitor 99.96%
    Tubeimoside I is an orally active HSPD1 inhibitor. Tubeimoside I inhibits NF-κB, MAPK, as well as regulates eNOS-VEGF. Tubeimoside I induces cytoprotective Autophagy via an Akt-mediated pathway. Tubeimoside I inhibits proinflammatory cytokine (IL-6 and IL-1β) production. Tubeimoside I exhibits anti-inflammatory activities. Tubeimoside I promotes angiogenesis and improves sepsis symptoms. Tubeimoside I is used in the research of inflammatory diseases, various cancers, sepsis and ischemic diseases.
    Tubeimoside I
  • HY-N0629
    Maslinic acid
    Inhibitor 99.87%
    Maslinic acid can inhibit the DNA-binding activity of NF-κB p65 and abolish the phosphorylation of IκB-α, which is required for p65 activation.
    Maslinic acid
  • HY-120501
    B022
    Inhibitor 99.27%
    B022 is a potent and selective NF-κB-inducing kinase (NIK) inhibitor (Ki of 4.2 nM; IC50=15.1 nM). B022 protects liver from toxin-induced inflammation, oxidative stress, and injury. B022 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    B022
  • HY-126397
    MnTBAP chloride
    Inhibitor 98.0%
    MnTBAP chloride is a superoxide dismutase (SOD) mimetic and peroxynitrite scavenger. MnTBAP chloride is a manganic porphyrin complex and has anti-oxidative property. MnTBAP chloride mediates anti-inflammatory effects through upregulation of BMPR-II and inhibition of the NFκB signaling. MnTBAP chloride has the potential for the fibrotic response in chronic kidney diseases (CKDs) research.
    MnTBAP chloride
  • HY-112433
    NIK SMI1
    Inhibitor 99.92%
    NIK SMI1 is a potent, selective NF-κB inducing kinase (NIK) inhibitor, which inhibits NIK-catalyzed hydrolysis of ATP to ADP with IC50 of 0.23±0.17 nM. NIK SMI1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    NIK SMI1
  • HY-135317
    Emavusertib
    Inhibitor 99.97%
    Emavusertib is an orally active inhibitor for IRAK4 (IC50=57 nM) and FLT3. Emavusertib 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 exhibits antitumor activity in mouse model
    Emavusertib
  • HY-N0250
    Saikosaponin D
    Inhibitor 99.81%
    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
  • HY-N0587
    Demethylzeylasteral
    Inhibitor 99.92%
    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 [1][2].
    Demethylzeylasteral
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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