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-N8903
    Mumefural
    Inhibitor
    Mumefural is a bioactive component of the processed fruit of Prunus mume Sieb. Mumefural inhibits platelet aggregation. Mumefural shows anti-thrombotic effects and ameliorates cognitive impairment.
    Mumefural
  • HY-N9971R
    Hentriacontane (Standard)
    Inhibitor
    Hentriacontane (Standard) is the analytical standard of Hentriacontane. This product is intended for research and analytical applications. Hentriacontane is a long-chain alkane. Hentriacontane exerts anti-inflammatory effects by inhibiting the NF-κB pathway. Hentriacontane has anti-inflammatory, antitumor and antibacterial activities.
    Hentriacontane (Standard)
  • HY-176127
    JX10
    Inhibitor
    JX10 is a senomorphic agent. JX10 suppresses the expression of p38 MAPK and NF-κB. JX10 exhibits competent antiaging effects in C. elegans, senescent cells, and aged mice.
    JX10
  • HY-N13798
    ADHPE
    Inhibitor
    ADHPE is a stabilizer of 14-3-3σ and p65 protein complex. ADHPE inhibits NF-κB (p65) signaling pathway and reduces the inflammatory response. ADHPE can be used for pediatric pneumonia-related acute lung injury and acute respiratory distress syndrome study.
    ADHPE
  • HY-144744
    NF-κB-IN-3
    Inhibitor
    NF-κB-IN-3 (Compound 2) is a NF-κB inhibitor with an IC50 of 0.70 µM. NF-κB-IN-3 can be used as an antitumor agent.
    NF-κB-IN-3
  • HY-149696
    IR-Crizotinib
    Inhibitor
    IR-Crizotinib is a NF-κB-inducing kinase (NIK) inhibitor that crosses the blood-brain barrier and fluorescently localizes intracranial glioblastoma (GBM) in mice (IC50=3.381 μM). IR-Crizotinib is conjugated from the near-infrared dye IR-786 and the NF-κB-inducing kinase (NIK) inhibitor Crizotinib. IR-Crizotinib can effectively inhibit the growth and invasion of glioma in vitro and in vivo and can be used in cancer research.
    IR-Crizotinib
  • HY-180291
    Anti-inflammatory agent 109
    Inhibitor
    Anti-inflammatory agent 109 (Compound 2m) is an anti-inflammatory agent. Anti-inflammatory agent 109 directly interacts with p65, attenuates aberrant activation of the NF-κB pathway. Anti-inflammatory agent 109 significantly suppresses the release of key pro-inflammatory mediators, including IL-1β, COX-2, and iNOS. Anti-inflammatory agent 109 conferres robust protection against LPS-induced acute liver injury in septic mice.
    Anti-inflammatory agent 109
  • HY-173488
    NF-κB/HIF-1α-IN-1
    Inhibitor
    NF-κB/HIF-1α-IN-1 (compound 9c) is a potent blocker of the NF-κB activation pathway and demonstrates selective anti-fibrotic activity. NF-κB/HIF-1α-IN-1 shows no significant cytotoxicity in NCI tumor cell lines. In rat models. NF-κB/HIF-1α-IN-1 has been shown to effectively ameliorate liver fibrosis by inhibiting the expression levels of NF-κB and HIF-1α, while simultaneously inducing the activation of Nrf2.
    NF-κB/HIF-1α-IN-1
  • HY-P10966
    Tat-IKIP (46-60)
    Inhibitor
    Tat-IKIP (46-60) is a IκB kinase (IKK)-targeting membrane-penetrating peptide. Tat-IKIP (46-60) inhibits IKK activation and NF-κB targeted gene expression by disrupting the IKKβ/NEMO complex. Tat-IKIP (46-60) significantly reduces DSS (HY-116282)-induced acute inflammation in inflammatory bowel disease (IBD) mice model and attenuates Zymosan-induced acute arthritis in acute arthritis model (AAM). Tat-IKIP (46-60) can be used for inflammatory diseases research, such as IBD, pancreatitis and rheumatoid arthritis.
    Tat-IKIP (46-60)
  • HY-B0026R
    Ceftiofur hydrochloride (Standard)
    Inhibitor
    Ceftiofur hydrochloride (Standard) is the analytical standard of Ceftiofur hydrochloride (HY-B0026). This product is intended for research and analytical applications. Ceftiofur hydrochloride is a cell wall synthesis inhibitor that targets bacterial penicillin-binding proteins (PBPs) and has anti-inflammatory effects in endotoxemia. Ceftiofur hydrochloride exerts bactericidal effects by inhibiting the synthesis of bacterial cell wall peptidoglycan, leading to bacterial cell lysis. Ceftiofur hydrochloride also inhibits the activation of NF-κB and MAPKs, thereby reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6.
    Ceftiofur hydrochloride (Standard)
  • HY-N13338
    Avicin D
    Inhibitor
    Avicin D is a plant triterpenoid. Avicin D induces Autophagy by activation of AMPK. Avicin D inhibits mTOR and S6 kinase activity. Avicin D selectively induces Apoptosis and downregulates p-STAT-3, bcl-2, and Survivin. Avicin D has properties of being a selective Glucocorticoid receptor modulator. Avicin D inhibits NF-κB activation. Avicin D shows anti-tumor effects against cutaneous T-cell lymphomas.
    Avicin D
  • HY-B0808S1
    Oxaprozin-d5
    Inhibitor
    Oxaprozin-d5 is deuterium labeled Oxaprozin. Oxaprozin is an inhibitor of both COX-1 and COX-2 with IC50s of 2.2 μM and 36 μM for human platelet COX-1 and IL-1-stimulated human synovial cell COX-2, respectively. Oxaprozin also inhibits the activation of NF-κB.
    Oxaprozin-d<sub>5</sub>
  • HY-136271
    MJ33
    Inhibitor
    MJ-33 is a competitive phospholipase A₂ (PLA₂) inhibitor with an IC50 of 0.3 μM. MJ-33 inhibits the activation of NOX2 by blocking the PLA₂ activity of Prdx6, thereby reducing the production of ROS. MJ-33 effectively inhibits the activity of acidic PLA₂ (pH 4.0), reduces the degradation of pulmonary surfactant phosphatidylcholine (PC), but has no effect on alkaline PLA₂ (pH 8.5). MJ-33 significantly alleviates lung oxidative damage induced by ischemia-reperfusion (I/R). MJ-33 significantly inhibits the invasive, migratory and adhesive abilities of prostate cancer cells by suppressing the MAPK, AKT, NF-κB and AP-1 signaling pathways. MJ-33 can be used to study ROS-related diseases and prostate cancer.
    MJ33
  • HY-108538
    Ethacrynic acid D5
    Inhibitor
    Ethacrynic acid D5 is a deuterium labeled Ethacrynic acid. Ethacrynic acid is a diuretic. Ethacrynic acid is an inhibitor of glutathione S-transferases (GSTs). Ethacrynic acid is a potent inhibitor of NF-kB-signaling pathway, and also modulates leukotriene formation. Ethacrynic acid also inhibits L-type voltage-dependent and store-operated calcium channel, leading to relaxation of airway smooth muscle (ASM) cells. Ethacrynic acid has anti-inflammatory properties that reduces the retinoid-induced ear edema in mice.
    Ethacrynic acid D5
  • HY-18325A
    AN-3485 hydrochloride
    Inhibitor
    AN-3485 hydrochloride is a benzoxaborole analogue and an orally active antagonist of the Toll-like pathway. AN-3485 hydrochloride can inhibit TLR-mediated inflammatory cytokine secretion and has significant anti-inflammatory activity. In addition, AN-3485 hydrochloride also has certain anti-tumor activity.
    AN-3485 hydrochloride
  • HY-149580
    NF-κB-IN-12
    Inhibitor
    NF-κB-IN-12 (compound 3h) is a potent NF-κB inhibitor, with an IC50 of 1.02 μM. NF-κB-IN-12 can be used for acute lung injury research.
    NF-κB-IN-12
  • HY-126232
    Verproside
    Inhibitor
    Verproside, a catalpol derivative iridoid glycoside isolated from the genus Pseudolysimachion, represses TNF-α -induced MUC5AC expression by inhibiting NF-κB activation via the IKK/IκB signaling cascade. Verproside has potent anti-inflammatory, antioxidant, antinociceptive and anti-asthmatic activities. Verproside has the potential for the study of chronic obstructive pulmonary disease (COPD).
    Verproside
  • HY-P992200
    Anti-CD146 Antibody (AA98)
    Inhibitor
    Anti-CD146 Antibody (AA98) is an antibody targeting CD146 and an angiogenesis inhibitor. Anti-CD146 Antibody (AA98) blocks the dimerization of CD146 as well as its downstream PI3K/AKT, p38 MAPK and NF-κB signaling pathways; it inhibits the expression of MMP9 and ICAM1, epithelial-mesenchymal transition (EMT), and the proliferation, migration and tube formation of endothelial cells. Anti-CD146 Antibody (AA98) enhances radiation-induced cancer cell apoptosis and survival inhibition, reduces tumor microvessel density, and suppresses tumor growth, invasion and vasculogenic mimicry. Anti-CD146 Antibody (AA98) can be used in research related to cervical cancer, liver cancer, malignant phyllodes tumor of the breast, uveal melanoma, leiomyosarcoma, pancreatic cancer, other tumors and angiogenesis.
    Anti-CD146 Antibody (AA98)
  • HY-N0041R
    Ginsenoside Rb3 (Standard)
    Inhibitor
    Ginsenoside Rb3 (Standard) is the analytical standard of Ginsenoside Rb3. This product is intended for research and analytical applications. Ginsenoside Rb3 is extracted from steamed Panax ginseng C. A. Meyer. Ginsenoside Rb3 exhibits inhibitory effect on TNFα-induced NF-κB transcriptional activity with an IC50 of 8.2 μM in 293T cell lines. Ginsenoside Rb3 also inhibits the induction of COX-2 and iNOS mRNA.
    Ginsenoside Rb3 (Standard)
  • HY-171656
    G721-0282
    Inhibitor 99.96%
    G721-0282 is an orally active CHI3L1 inhibitor. G721-0282 can reduce the expression of inflammatory proteins and cytokines. G721-0282 inhibits the activation of the NF-κB signaling pathway. G721-0282 inhibits neuroinflammation and reduces anxious behavior. G721-0282 significantly inhibits the proliferation of osteosarcoma (OS) cells by suppressing the STAT3 signaling pathway. G721-0282 induces OS cell apoptosis by upregulating pro-apoptotic protein levels and downregulating anti-apoptotic protein levels. G721-0282 can be used for researches on neuroinflammatory conditions and cancer.
    G721-0282
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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