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-N0141R
    Parthenolide (Standard)
    Inhibitor
    Parthenolide (Standard) is the analytical standard of Parthenolide. This product is intended for research and analytical applications. Parthenolide is a sesquiterpene lactone found in the medicinal herb Feverfew. Parthenolide exhibits anti-inflammatory activity by inhibiting NF-κB activation; also inhibits HDAC1 protein without affecting other class I/II HDACs.
    Parthenolide (Standard)
  • HY-N11892
    7-O-Methylaloesinol
    Inhibitor
    7-O-Methylaloesinol is a chromone derivative. 7-O-Methylaloesinol shows significant inhibitory effects against TNFα-induced NF-κB transcriptional activity with an IC50 value of 29.07 μM.
    7-O-Methylaloesinol
  • HY-149838
    NF-κB-IN-9
    Inhibitor
    NF-κB-IN-9 is a nuclear factor kappa B (NF-κB) targeting sonosensitizer (λex/λem=489/628 nm). NF-κB-IN-9 exhibits strong inhibition on NF-κB signaling due to its two resveratrol units in one molecule. NF-κB-IN-9 has anti-tumor activity and shows remarkable sonocytotoxicity against cancer cells. NF-κB-IN-9 has biosafety in eenograft mice model.
    NF-κB-IN-9
  • HY-114335
    Triphala
    Inhibitor
    Triphala, an Ayurvedic polyherbal formulation comprising of equiproportional fruit parts of Terminalia chebula, Terminalia bellerica, and Phyllanthus emblica. Triphala inhibits NF-κB activation. Triphala exerts antifungal action. Anti-adipogenic, anti-inflammatory, and anti-neoplastic activities.
    Triphala
  • HY-162538
    LC-MI-3
    Inhibitor
    LC-MI-3 is an orally active and potent interleukin-1 receptor-associated kinase 4 (IRAK4) PROTAC degrader, with a DC50 of 47.3 nM. LC-MI-3 effectively inhibits the activation of downstream NF-κB signaling. LC-MI-3 can be used for the research of acute and chronic inflammatory skin. (Blue: VHL ligand, Black: linker, Pink: CRBN ligand (HY-14658)).
    LC-MI-3
  • HY-P991432
    VTX-0811
    Activator
    VTX-0811 is a human IgG4 monoclonal antibody (mAb) targeting PSGL1/CD162. VTX-0811 up-regulates TNF-α/NF-κB and chemokine-mediated signaling and down-regulates oxidative phosphorylation, fatty acid metabolism, and Myc signaling pathways. VTX-0811 increases the proportion of CD8+ T cells among infiltrating T cells. VTX-0811 has antitumor activity in a humanized mouse PDX model of melanoma.
    VTX-0811
  • HY-125740R
    Malvidin-3-glucoside chloride (Standard)
    Inhibitor
    Malvidin-3-glucoside (Malvidin-3-O-glucoside; Oenin) chloride (Standard) is the analytical standard of Malvidin-3-glucoside chloride (HY-125740). This product is intended for research and analytical applications. Malvidin-3-glucoside chloride is an orally active inhibitor of the NF-κB pathway, which blocks inflammatory responses induced by TNF-α, reduces IκB-α degradation and p65 nuclear translocation, and upregulates endothelial nitric oxide synthase eNOS to increase NO production. Malvidin-3-glucoside chloride exerts anti-inflammatory and antioxidant effects by inhibiting pro-inflammatory molecules such as MCP-1, ICAM-1, and IL-6, and regulating intestinal microorganisms and metabolites, while protecting endothelial cells and improving intestinal microecological dysbiosis under inflammatory conditions. Malvidin-3-glucoside chloride can be used to study chronic inflammatory-related diseases such as atherosclerosis and inflammatory bowel disease, and has the potential to prevent vascular inflammation and improve intestinal health.
    Malvidin-3-glucoside chloride (Standard)
  • HY-32735R
    Triptolide (Standard)
    Inhibitor
    Triptolide (Standard) is the analytical standard of Triptolide. This product is intended for research and analytical applications. Triptolide is a diterpenoid triepoxide extracted from the root of Tripterygium wilfordii with immunosuppressive, anti-inflammatory, antiproliferative and antitumour effects. Triptolide is a NF-κB activation inhibitor.
    Triptolide (Standard)
  • HY-B0765R
    Dehydroepiandrosterone sulfate sodium (Standard)
    Inhibitor
    Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) sodium salt (Standard) is the analytical standard of Dehydroepiandrosterone sulfate sodium salt (HY-B0765). This product is intended for research and analytical applications. Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) is a neurosteroid and the main secretion product of the adrenal gland. Dehydroepiandrosterone sulfate has both non-competitive antagonist activity of GABAA receptor and agonist activity of σ1 receptor. Dehydroepiandrosterone sulfate can partially penetrate the blood-brain barrier, inhibit GABAA receptor-mediated chloride influx, enhance NMDA receptor activity through σ1 receptors, exert anti-inflammatory, anti-glucocorticoid and antidepressant effects, and increase convulsive sensitivity. Dehydroepiandrosterone sulfate participates in neuroprotection, neurite growth regulation and catecholamine secretion regulation, and can be used in the study of depression, post-traumatic stress disorder (PTSD), Alzheimer's disease, etc. Dehydroepiandrosterone sulfate may also be a biomarker for cardiovascular disease mortality, and its concentration is independently and negatively correlated with mortality.
    Dehydroepiandrosterone sulfate sodium (Standard)
  • HY-N0316R
    Mollugin (Standard)
    Inhibitor
    Mollugin (Standard) is the analytical standard of Mollugin. This product is intended for research and analytical applications. Mollugin is an orally active and potent NF-κB inhibitor. Mollugin induces S-phase arrest of HepG2 cells, and increased intracellular reactive oxygen species (ROS) levels. Mollugin induces DNA damage in HepG2 cells, as well as an increase in the expression of p-H2AX. Mollugin shows anti-cancer effect by inhibiting TNF-α-induced NF-κB activation. Mollugin enhances the osteogenic action of BMP-2 (bone morphogenetic protein 2) via the p38-Smad signaling pathway.
    Mollugin (Standard)
  • HY-152945
    Antiproliferative agent-22
    Inhibitor
    Antiproliferative agent-22 (compound 2) is an anticancer agent. Antiproliferative agent-22 shoes anti-proliferative activities against MCF-7, MDA-MB-231 and MDA-MB-468 cells with IC50 values of 6.2 μM, 3.3 μM and 3.3 μM, respectively.
    Antiproliferative agent-22
  • HY-W701772
    2-Oleoylglycerol-d5
    2-Oleoylglycerol-d5 (2-OG-d5) is the deuterium labeled 2-Oleoylglycerol (HY-W011121). 2-Oleoylglycerol (2-OG) is a lipid found in the diet. It is a GPR119 agonist, with an EC50 value of 2.5 μM in activating hGPR119 in transiently transfected COS-7 cells. 2-Oleoylglycerol enhances the inflammatory response of macrophages and promotes fibrosis by activating the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway. It also stimulates glucagon-like peptide 1 (GLP-1) secretion in vivo. 2-Oleoylglycerol is expected to be used in the research of non-alcoholic steatohepatitis (NASH) .
    2-Oleoylglycerol-d<sub>5</sub>
  • HY-N6602R
    α-Solanine (Standard)
    Inhibitor
    α-Solanine (Standard) is the analytical standard of α-Solanine. This product is intended for research and analytical applications. α-solanine, a bioactive component and one of the major steroidal glycoalkaloids in Solanum nigrum, has been observed to inhibit growth and induce apoptosis in cancer cells.
    α-Solanine (Standard)
  • HY-142100
    Licoagrochalcone C
    Inhibitor
    Licoagrochalcone C, a flavonoid, reveals efficacious inhibitory activity on NF-κB transcription. Licoagrochalcone C shows significant inhibitory activity on LPS (HY-D1056)-induced NO production.
    Licoagrochalcone C
  • HY-N0045R
    Ginsenoside Rg1 (Standard)
    Inhibitor
    Ginsenoside Rg1 (Standard) is the analytical standard of Ginsenoside Rg1. This product is intended for research and analytical applications. Ginsenoside Rg1 is one of the major active components of Panax ginseng. Ginsenoside Rg1 ameliorates the impaired cognitive function, displays promising effects by reducing cerebral Aβ levels. Ginsenoside Rg1 also reduces NF-κB nuclear translocation.
    Ginsenoside Rg1 (Standard)
  • HY-N2098R
    Obtusifolin (Standard)
    Inhibitor
    Obtusifolin (Standard) is the analytical standard of Obtusifolin. This product is intended for research and analytical applications. Obtusifolin, isolated from the seeds of Cassia obtusifolia, regulates the gene expression and production of MUC5AC mucin in airway epithelial cells via inhibiting NF-kB pathway. Obtusifolin suppresses phthalate esters-induced breast cancer bone metastasis by targeting parathyroid hormone-related protein.
    Obtusifolin (Standard)
  • HY-120269
    CAY10512
    Inhibitor
    CAY10512 is an inhibitor of NF-κB. CAY10512 can suppress the upregulation of NF-κB-sensitive proinflammatory miRNAs (miRNA-9, miRNA-125b, miRNA-146a, miRNA-155) in cerebrospinal fluid and extracellular fluid, and can be used for research on Alzheimer's disease.
    CAY10512
  • HY-D0162R
    Malachite green hemioxalate (Standard)
    Inhibitor
    Malachite green hemioxalate (Standard) is the analytical standard of Malachite green hemioxalate (HY-D0162). This product is intended for research and analytical applications. Malachite green hemioxalate is a triphenylmethane dye which can be used to detect the release of phosphate in enzymatic reactions. Malachite green hemioxalate has antimicrobial activity, which is attributed to inhibition of intracellular enzymes, intercalation into DNA, and/or interaction with cellular membranes. Malachite green hemioxalate is also a potent and selective inhibitor of IKBKE, and inhibits its downstream targets such as IκBα, p65 and IRF3. Malachite green hemioxalate exhibits antitumor activity in vitro and in vivo.
    Malachite green hemioxalate (Standard)
  • HY-W654377
    Triptolide-d3(major) (>90%)
    Triptolide-d3 (major) (>90%) is the deuterium labeled Triptolide (HY-32735). Triptolide is a diterpenoid triepoxide extracted from the root of Tripterygium wilfordii with immunosuppressive, anti-inflammatory, antiproliferative and antitumour effects. Triptolide is a NF-κB activation inhibitor.
    Triptolide-d<sub>3</sub>(major) (>90%)
  • HY-124557
    Mahanimbine
    Inhibitor
    Mahanimbine is an orally active alkaloid from Murraya koenigii. Mahanimbine inhibits progression of high-fat diet (HFD)-induced metabolic complications in mice.
    Mahanimbine
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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