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-W001925
    7-Methoxy-1-tetralone
    Inhibitor 99.93%
    7-Methoxy-1-tetralone is a potent antitumor agent. 7-Methoxy-1-tetralone inhibits cancer cell proliferation and migration, and induces hepatocellular carcinoma cell (HCC) apoptosis. 7-Methoxy-1-tetralone decreased the protein levels of NF-κB, matrix metallopeptidase 2 (MMP2)/MMP9, and p-AKT. 7-Methoxy-1-tetralone showed antitumor activity in nude mice and had no effect on body weight and liver, spleen and organ index.
    7-Methoxy-1-tetralone
  • HY-14654S1
    Aspirin-d4
    Inhibitor 98.41%
    Aspirin-d4 is the deuterium labeled Aspirin (HY-14654). Aspirin (Acetylsalicylic acid) is an orally active, potent and irreversible inhibitor of cyclooxygenase COX-1 and COX-2, with IC50 values of 5 and 210 μg/mL, respectively. Aspirin induces apoptosis. Aspirin inhibits the activation of NF-κB. Aspirin also inhibits platelet prostaglandin synthetase, and can prevent coronary artery and cerebrovascular thrombosis.
    Aspirin-d<sub>4</sub>
  • HY-108292
    Propacetamol hydrochloride
    Inhibitor 99.74%
    Propacetamol hydrochloride is an orally active prodrug of paracetamol and an inducer of acute liver injury models, with multiple properties including antinociception, antioxidation and gastroprotection. Propacetamol hydrochloride potentiates Tramadol and attenuates Aspirin (HY-14654)-induced gastric mucosal damage and lipid peroxidation. Under specific conditions, Propacetamol hydrochloride also acts as a hepatotoxic inducer, triggering acute liver injury, oxidative stress and apoptosis, with strain differences in toxicity sensitivity. Propacetamol hydrochloride can be used in the research of acute liver injury, drug-induced hepatotoxicity and gastric mucosal damage.
    Propacetamol hydrochloride
  • HY-N1731
    2′-Hydroxy-5′-methoxyacetophenone
    Inhibitor 99.96%
    2'-Hydroxy-5'-methoxyacetophenone is an acetophenone derivative with acaricidal activities. 2'-Hydroxy-5'-methoxyacetophenone attenuates the inflammatory response via NF-κB signaling pathway. 2'-Hydroxy-5'-methoxyacetophenone exhibits significant inhibitory activity against α-amylase, collagenase and aldose reductase (AR) with IC50s of 0.928, 3.264 and 20.046 μM, highlighting its potential in combating diabetes. 2'-Hydroxy-5'-methoxyacetophenone exhibits anti-ovarian cancer activity.
    2′-Hydroxy-5′-methoxyacetophenone
  • HY-15530
    CID-2858522
    Inhibitor 99.78%
    CID-2858522 is a highly potent and selective antigen receptor-mediated NF-κB activation inhibitor with an IC50 of 70 nM.
    CID-2858522
  • HY-175222
    GlcNAc-MurNAc
    Inhibitor
    GlcNAc-MurNAc, a disaccharide, is a TLR4 agonist with a Kd of 383 μM for murine TLR4. GlcNAc-MurNAc directly binds to TLR4 and activates its downstream NF-κB and IRF pathways. GlcNAc-MurNAc improves Dextran sulfate sodium salt (DSS) (HY-116282C)-induced colitis in mice through a TLR4-dependent mechanism. GlcNAc-MurNAc can be used for the study of inflammatory bowel disease.
    GlcNAc-MurNAc
  • HY-157331
    DCZ5418
    Inhibitor 99.02%
    DCZ5418 is an inhibitor of TRIP13. DCZ5418 has anti-multiple myeloma activity in vitro and in vivo.
    DCZ5418
  • HY-B0289
    Erdosteine
    Inhibitor 99.54%
    Erdosteine inhibits lipopolysaccharide (LPS)-induced NF-κB activation. Erdosteine has muco-modulatory, anti-bacterial, anti-inflammatory and anti-oxidant effects.
    Erdosteine
  • HY-N2041R
    Myristic acid (Standard)
    Activator
    Myristic acid (Standard) is the analytical standard of Myristic acid. This product is intended for research and analytical applications. Myristic acid is an orally active saturated 14-carbon fatty acid found in most animal and plant fats, especially milk fat coconut oil, palm oil and nutmeg oil. Myristic acid exerts anti-inflammatory activity through the NF-κB pathway. Myristic acid has antibacterial, anti-inflammatory and analgesic properties.
    Myristic acid (Standard)
  • HY-P990208
    Anti-Mouse IL-9 Antibody (9C1)
    Inhibitor
    Anti-Mouse IL-9 Antibody (9C1) is an anti-mouse IL-9 IgG2a monoclonal antibody. Anti-Mouse IL-9 Antibody (9C1) can reduce the activation of NF-κB signaling pathway and decrease the infiltration of inflammatory cells. Anti-Mouse IL-9 Antibody (9C1) effectively reduces Th9 cell-mediated allergic reactions and anti-tumor effects. Anti-Mouse IL-9 Antibody (9C1) can be used for researches on inflammation, infection conditions and cancer such as parasitic infections, allergic reactions, breast cancer and osteosarcoma.
    Anti-Mouse IL-9 Antibody (9C1)
  • HY-P5523A
    iE-DAP dihydrochloride
    Activator 99.72%
    iE-DAP dihydrochloride is a Nod1 agonist. iE-DAP dihydrochloride activates NOD1, which in turn activates the NF-κB signaling pathway and MLCK signaling pathway, inducing cellular inflammatory responses and tight junction disruption. iE-DAP dihydrochloride downregulates the expression of ZO-1 and Occludin genes. iE-DAP dihydrochloride increases the secretion of IL-6, GRO-α, MCP-1, IL-8 and MIP-1β in term human trophoblast cell cultures. iE-DAP dihydrochloride triggers preterm birth in pregnant mice, reduces fetal body weight, and induces fetal inflammation. iE-DAP dihydrochloride can be used in studies related to mastitis and preterm birth.
    iE-DAP dihydrochloride
  • HY-W324435
    2,4-Dinitrobenzenesulfonic acid sodium salt
    Activator 99.98%
    2,4-Dinitrobenzenesulfonic acid (DNBS; DNBSO) sodium salt (Sodium 2,4-dinitrobenzenesulfonate) is a classic colitis inducer that relies on activation of the NF-κB p65/COX-2/p38 pathway. As a hapten, 2,4-Dinitrobenzenesulfonic acid sodium salt stimulates the production of immune responses in colonic tissues, triggers oxidative stress and inflammatory reactions, and thereby leads to colonic injury. 2,4-Dinitrobenzenesulfonic acid sodium salt successfully induces models of colitis and ulcerative colitis in rats, causing pathological changes such as ulcers, edema, stenosis, shortening and organ adhesion in the distal colon, along with significant increases in the levels of inflammatory indicators and endoplasmic reticulum stress marker proteins. 2,4-Dinitrobenzenesulfonic acid sodium salt is widely used in studies on the mechanisms related to colitis and ulcerative colitis.
    2,4-Dinitrobenzenesulfonic acid sodium salt
  • HY-P99635
    Gatralimab
    Inhibitor
    Gatralimab (GZ-402668) is an IgG1 anti-CD52 monoclonal antibody.
    Gatralimab
  • HY-107352
    Fosfenopril
    Inhibitor 99.85%
    Fosfenopril (Fosinoprilat) is a potent angiotensin converting enzyme (ACE) inhibitor. Fosfenopril alleviates lipopolysaccharide (LPS)-induced inflammation by inhibiting TLR4/NF-κB signaling in monocytes.
    Fosfenopril
  • HY-W097625
    6-Methoxyflavone
    Inhibitor 99.73%
    6-Methoxyflavone is an orally active methoxyflavone. 6-Methoxyflavone suppresses neuroinflammation in microglia through the inhibition of TLR4/MyD88/p38 MAPK/NF-κB dependent pathways and the activation of HO-1/NQO-1 signaling. 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells. 6-Methoxyflavone inhibits NFAT Translocation into the nucleus and suppresses T cell activation. 6-Methoxyflavone partially restores chronic ethanol-induced behavioral deficits in mice. 6-Methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression. 6-Methoxyflavone can be used for the study of cancer, inflammation and neurological diseases.
    6-Methoxyflavone
  • HY-174138
    NF-κB degrader 1
    Degrader 99.92%
    NF-κB degrader 1 (Compound MD-1) is a NF-κB1 p105 subunit degrader. NF-κB degrader 1 shows anti-inflammatory activity (IC50 for inhibiting TNF-α is 2.02 μM, and for inhibiting NO is 5.40 μM). NF-κB degrader 1 induces p105 degradation dependent on the Cullin-RING ligase (CRL) SCFBTCP, suppressing NF-κB transcriptional activity. NF-κB degrader 1 is promising for research of inflammation-related diseases.
    NF-κB degrader 1
  • HY-N7043
    Isosilybin A
    Inhibitor 99.63%
    Isosilybin A is a PPARγ agonist that can be isolated from silymarin. Isosilybin A activates extrinsic and intrinsic pathways of apoptosis through targeting of the Akt-NF-kB-AR axis. Isosilybin A can relieve the inflammatory response in the rosacea model via inhibiting Erk and p38 signaling pathways and M1 macrophage polarization, with its targets related to RELA and VEGFA. Isosilybin A has anti-prostate cancer (PCA) activity[1][2][3].
    Isosilybin A
  • HY-107566
    Conessine
    Inhibitor 99.87%
    Conessine is an orally active and BBB-penetrable selective histamine H3 receptor antagonist. The pKi values of Conessine for rat and human H3 receptors are 7.61 and 8.27, respectively. Conessine is an inhibitor of the multidrug efflux pump system in Pseudomonas aeruginosa and can enhance the activity of antibiotics. Conessine has antimalarial activity. Conessine can also be used in the research of muscle atrophy.
    Conessine
  • HY-15027S1
    5-Aminosalicylic acid-d3
    99.38%
    5-Aminosalicylic acid-d3 is the deuterium labeled 5-Aminosalicylic Acid. 5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB.
    5-Aminosalicylic acid-d<sub>3</sub>
  • HY-N2282
    Zingiberen newsaponin
    Inhibitor 99.68%
    Zingiberen Newsaponin (Zingiberensis newsaponin) is an orally active type of steroid saponin compound. Zingiberen Newsaponin exerts anti-hepatocellular carcinoma (HCC) effects by inhibiting autophagy and the AKR1C1/JAK2/STAT3 pathway. Zingiberen Newsaponin activates oxidative stress (upregulates ROS and MDA) and mitochondrial pathways, promoting cancer cell apoptosis. Zingiberen Newsaponin alleviates cerebral ischemia-reperfusion (I/R) injury by decreasing the concentration of pro-inflammatory cytokines and inhibits NF-κB. Zingiberen Newsaponin can enhance the activity of SOD, eliminate free radicals and protect nerve cells. Zingiberen Newsaponin induces platelet aggregation.
    Zingiberen newsaponin
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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