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-W770410
    9-PAHSA-13C4
    Inhibitor 99.9%
    9-PAHSA-13C4 is 13C-labeled 9-PAHSA. 9-PAHSAis an orally active endogenous GPR120 agonist (EC50=18 μM). 9-PAHSAsignificantly inhibits LPS-induced inflammatory responses by blocking the NF-κB pathway. 9-PAHSAinduces adipocyte browning, enhances glucose uptake and reduces lipid accumulation, while improving mitochondrial function and the survival rate of steatotic hepatocytes. In terms of neuroprotection, 9-PAHSAregulates the expression of REST and BDNF in the prefrontal cortex of diabetic mice, and effectively prevents spatial working memory deficits and abnormal social behaviors. 9-PAHSAdoes not directly regulate insulin secretion or improve systemic insulin sensitivity, and possesses specific anti-inflammatory, metabolic regulatory and neuroprotective properties. 9-PAHSAcan be used in the research of diabetes-related cognitive impairment, obesity and non-alcoholic fatty liver disease.
    9-PAHSA-<sup>13</sup>C<sub>4</sub>
  • HY-B1773AS4
    Sodium propionate-d5
    Inhibitor 99.91%
    Sodium propionate-d5 is the deuterium labeled Propionate sodium (HY-B1773A). Sodium propionate is an orally active short-chain fatty acid. Sodium propionate can be produced by intestinal bacteria from the metabolism of dietary fiber. Sodium propionate increases PPAR-γ, inhibits NF-κB activation, and reduces COX-2 expression and NO production. Sodium propionate also induces Apoptosis and Autophagy. Sodium propionate reduces HSV-1-induced keratitis. Sodium propionate has anticancer effects against glioblastoma. Sodium propionate exhibits neuroprotective, antioxidant, and anti-inflammatory activities. Sodium propionate can be used in the research of spinal cord injury and Alzheimer's disease.
    Sodium propionate-d<sub>5</sub>
  • HY-154825
    20-Hydroxyvitamin D3
    Inhibitor ≥98.0%
    20-Hydroxyvitamin D3 (20(OH)D3), a product of vitamin D3 hydroxylation, is a noncalcemic immunomodulator. 20-Hydroxyvitamin D3 binds to vitamin D receptor (VDR), activates VDR and aryl hydrocarbon receptor (AhR) signaling, stimulates CYP24A1 expression, and drives VDR nuclear translocation. 20-Hydroxyvitamin D3 inhibits NF-κB activity via IκBα upregulation. 20-Hydroxyvitamin D3 acts as a substrate for CYP27B1 and rat CYP24A1, undergoing hydroxylation to form dihydroxy-derivatives. 20-Hydroxyvitamin D3 inhibits cell proliferation, colony formation, migration, and tumor growth, and induces cell differentiation in cancer cells. 20-Hydroxyvitamin D3 can be used for the research of inflammatory and autoimmune diseases, melanoma, breast carcinomas, and hepatocarcinoma.
    20-Hydroxyvitamin D3
  • HY-N0344R
    Farrerol (Standard)
    Inhibitor
    Farrerol (Standard) is the analytical standard of Farrerol. This product is intended for research and analytical applications. Farrerol is a bioactive constituent of Rhododendron, with broad activities such as anti-oxidative, anti-inflammatory, anti-tumor, neuroprotective and hepatoprotective effects.
    Farrerol (Standard)
  • HY-143704S
    5-Aminosalicylic acid-13C6 hydrochloride
    Inhibitor 99.53%
    5-Aminosalicylic acid-13C6 hydrochloride?(Mesalamine-13C6 hydrochloride; 5-ASA-13C6 hydrochloride; Mesalazine-13C6 hydrochloride) is the 13C labeled 5-Aminosalicylic Acidhydrochloride. 5-Aminosalicylic acid-13C6 hydrochloride?acts as a PPARγ agonist, and also inhibits p21-activated kinase 1 (PAK1) and NF-κB.
    5-Aminosalicylic acid-<sup>13</sup>C<sub>6</sub> hydrochloride
  • HY-N19791
    6-Methoxymellein
    Inhibitor
    6-Methoxymellein, a phytoalexin, is a NF-κB inhibitor. 6-Methoxymellein reduces nuclear localization and DNA binding activity of NF-κB p65 and p50 subunits. 6-Methoxymellein decreases mRNA transcription and secretion of IL-6 and IL-8. 6-Methoxymellein reduces the proportion of CD44+/CD24 breast cancer cells, decreases expression of c-Myc, Sox-2 and Oct4, inhibits proliferation and migration of breast cancer cells, and reduces mammosphere growth. 6-Methoxymellein inhibits fungal growth of Trichophyton rubrum and Botrytis cinerea, and inhibits Trichophyton rubrum biofilm formation via hyphal disintegration. 6-Methoxymellein can be used for the research of breast cancer, tinea corporis, and carrot post-harvest storage rot.
    6-Methoxymellein
  • HY-W265314
    Arvelexin
    Inhibitor
    Arvelexin is a biologically active compound. Arvelexin can be found in Brassica rapa L. (Brassicaceae). Arvelexin inhibits NF-κB activation and the expressions of IL-8. Arvelexin inhibits colonic inflammation.
    Arvelexin
  • HY-N8407R
    Carminic acid (Standard)
    Inhibitor
    Carminic acid (Standard) is the analytical standard of Carminic acid (HY-N8407). This product is intended for research and analytical applications. Carminic acid is a widely used and orally active natural red pigment that can be used in industries such as food, cosmetics, and pharmaceuticals. In addition, carminic acid has anti-inflammatory and antioxidant activities.
    Carminic acid (Standard)
  • HY-N8707
    Homobutein
    Inhibitor 98.35%
    Homobutein a natural chalcones (can be found in many medicinal plants, fruits, vegetables, spices and nuts), is a potent HDACs/NF-κB dual inhibitor with IC50s of 190 and 38 μM, respectively. Homobutein also a chelator of iron (II and III) cations, shows various activities, including anticancer, anti-inflammatory, antiparasite and antioxidation.
    Homobutein
  • HY-B1619S
    Cromolyn-d5
    Inhibitor
    Cromolyn-d5 (Cromoglycate-d5) is the deuterium labeled Cromolyn (HY-B1619). Cromolyn (Cromoglycate) is an orally active GSK-3β inhibitor with an IC50 of 2.0 μM. Cromolyn is also a mast cell stabilizer that can inhibit the release of mediators from mast cells, regulate reflex bronchoconstriction, and reduce non-specific bronchial hyperreactivity, and Cromolyn can be used in the research of bronchial asthma. In addition, Cromolyn has multiple activities such as anti-inflammatory, anti-allergic, anti-histamine, anti-cancer, and neuroprotective effects.
    Cromolyn-d<sub>5</sub>
  • HY-117726
    WAY-169916
    Inhibitor 99.32%
    WAY-169916 is a pathway-selective ligand of ER (estrogen receptor) that acts by inhibiting NF-kB transcriptional activity. WAY-169916 has potent anti-inflammatory effect.
    WAY-169916
  • HY-N2908R
    Atraric acid (Standard)
    Inhibitor
    Atraric acid (Standard) is the analytical standard of Atraric acid. This product is intended for research and analytical applications. Atraric acid (Methyl atrarate) is a specific androgen receptor (AR) antagonist with anti-inflammatory and anticancer effects. Atraric acid represses the expression of the endogenous prostate specific antigen gene in both LNCaP and C4-2 cells. Atraric acid can also inhibit the synthesis of NO and cytokine, and suppress the MAPK-NFκB signaling pathway. Atraric acid can be used to research prostate diseases and inflammatory diseases[1][2].
    Atraric acid (Standard)
  • HY-135317B
    Emavusertib hydrochloride
    Inhibitor
    Emavusertib hydrochloride (CA-4948 tosylate) is the hydrochloride salt form of Emavusertib (HY-135317). Emavusertib hydrochloride is an orally active inhibitor for IRAK4 (IC50=57 nM) and FLT3. Emavusertib hydrochloride 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 hydrochloride exhibits antitumor activity in mouse model.
    Emavusertib hydrochloride
  • HY-N0168AS
    (Rac)-Hesperetin-d3
    Inhibitor
    (Rac)-Hesperetin-d3 is the 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-d<sub>3</sub>
  • HY-121309R
    Doxorubicinone (Standard)
    Inhibitor
    Doxorubicinone (Adriamycin aglycone) (Standard) is the analytical standard of Doxorubicinone. This product is intended for research and analytical applications. Doxorubicinone 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 (Standard)
  • HY-13559
    Atiprimod
    Inhibitor
    Atiprimod (Azaspirane) is a STAT3 inhibitor with antitumor, anti-inflammatory, and anti-angiogenic activities. Atiprimod blocks the signaling pathways of IL-6 and VEGF by inhibiting the phosphorylation of signal transducer and activator of STAT3. Atiprimod blocks the JAK-STAT signaling pathway by inhibiting the phosphorylation of JAK2 and JAK3. Atiprimod also inhibits cell proliferation, induces cell cycle arrest, and induces autophagy and apoptosis. Atiprimod triggers persistent ER stress-mediated apoptosis in breast cancer cells by activating the PERK/eIF2α/ATF4/CHOP axis and inhibiting the nuclear translocation of STAT3/NF-κB. Atiprimod shows great anti-tumor activities in tumor xenograft mouse models. Atiprimod can be used for the study of pituitary adenoma, breast cancer, multiple myeloma and acute myeloid leukemia (AML).
    Atiprimod
  • HY-B2082R
    Fursultiamine (Standard)
    Inhibitor
    Fursultiamine (Standard) is the analytical standard of Fursultiamine. This product is intended for research and analytical applications. Fursultiamine is a vitamin B1 derivative, has anti-nociceptive and antineoplastic activity. Fursultiamine can be used for vitamin B1 deficiency, osteoarthritis (OA) and cancer research.
    Fursultiamine (Standard)
  • HY-19667
    BMS-561392
    Inhibitor
    BMS-561392 (BMS-561392) is a selective ADAM17(TACE) inhibitor. BMS-561392 inhibits TNF-α secretion by regulating signaling pathways such as p44 MAPK and NF-κB. BMS-561392 also affects the survival of central nervous system-related cells including oligodendrocytes and microglia. BMS-561392 promotes microglial apoptosis, enlarges the injury area and exacerbates astrogliosis in a mouse spinal cord injury model. BMS-561392 can be used in research related to spinal cord injury and inflammatory diseases.
    BMS-561392
  • HY-144026S
    9-PAHSA-d9
    Inhibitor
    9-PAHSA-d9 is the deuterium labeled 9-PAHSA (HY-120657). 9-PAHSA is an orally active endogenous GPR120 agonist (EC50=18 μM). 9-PAHSA significantly inhibits LPS-induced inflammatory responses by blocking the NF-κB pathway. 9-PAHSA induces adipocyte browning, enhances glucose uptake and reduces lipid accumulation, while improving mitochondrial function and the survival rate of steatotic hepatocytes. In terms of neuroprotection, 9-PAHSA regulates the expression of REST and BDNF in the prefrontal cortex of diabetic mice, and effectively prevents spatial working memory deficits and abnormal social behaviors. 9-PAHSA does not directly regulate insulin secretion or improve systemic insulin sensitivity, and possesses specific anti-inflammatory, metabolic regulatory and neuroprotective properties. 9-PAHSA can be used in the research of diabetes-related cognitive impairment, obesity and non-alcoholic fatty liver disease.
    9-PAHSA-d<sub>9</sub>
  • HY-W062904
    Laquinimod sodium
    Inhibitor
    Laquinimod (ABR-215062) sodium, an orally available carboxamide derivative, is a potent immunomodulator which prevents neurodegeneration and inflammation in the central nervous system. Laquinimod sodium reduces astrocytic NF-κB activation to protect from Cuprizone-induced demyelination. Laquinimod sodium has the potential for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases research.
    Laquinimod sodium
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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