2. Signaling Pathways
  3. NF-κB
  4. NF-κB

NF-κB

Nuclear factor-κB; Nuclear factor-kappaB

NF-κB

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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.

NF-κB Isoform Specific Products:

NF-κB Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-10227G
    Bortezomib (GMP)
    		Inhibitor
    Bortezomib (GMP) (PS-341 (GMP)) is Bortezomib (HY-10227) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. Bortezomib (PS-341) is a reversible and selective proteasome inhibitor, and potently inhibits 20S proteasome (Ki=0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is the first proteasome inhibitor anticancer agent. Anti-cancer activity.
    Bortezomib (GMP)
  • HY-B1899R
    Taurodeoxycholic acid (Standard)
    		Inhibitor
    Taurodeoxycholic acid (Standard) is the analytical standard of Taurodeoxycholic acid. This product is intended for research and analytical applications. Taurodeoxycholate sodium salt is a bile salt-related anionic detergent. Taurodeoxycholic acid is formed in the liver by conjugation of deoxycholate with Taurine (HY-B0351). Taurodeoxycholic acid is used for isolation of membrane proteins including inner mitochondrial membrane proteins. Taurodeoxycholic acid (TDCA) exhibits anti-inflammatory and neuroprotective effects[1][2][3][9][10].
    Taurodeoxycholic acid (Standard)
  • HY-142958
    NF-κB-IN-2
    NF-κB-IN-2 inhibits TNF-α-induced canonical NF-κB signaling in PC-3 cells.
    NF-κB-IN-2
  • HY-N2350R
    Cynaropicrin (Standard)
    		Inhibitor
    Cynaropicrin (Standard) is the analytical standard of Cynaropicrin. This product is intended for research and analytical applications. Cynaropicrin is a sesquiterpene lactone which can inhibit tumor necrosis factor (TNF-α) release with IC50s of 8.24 and 3.18 μM for murine and human macrophage cells, respectively. Cynaropicrin also inhibits the increase of cartilage degradation factor (MMP13) and suppresses NF-κB signaling.
    Cynaropicrin (Standard)
  • 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-139719
    IMD-biphenylC
    		Modulator
    IMD-biphenylC is a novel imidazoquinolinone-NF-κB immunomodulator dimer that inhibits tumor proliferation while induces low systemic inflammation and reduces adjuvant toxicity.
    IMD-biphenylC
  • 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-122019
    ABD56
    ABD56 is a compound that induces osteoclast apoptosis and has the activity of inhibiting osteoclast formation and inducing apoptosis. ABD56 can inhibit osteoclast formation and induce apoptosis, and its mechanism is related to the inhibition of NFκB and ERK pathways.
    ABD56
  • HY-B1619R
    Cromolyn (Standard)
    		Inhibitor
    Cromolyn (Standard) is the analytical standard of Cromolyn. This product is intended for research and analytical applications. 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 (Standard)
  • 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-W707656
    Aspirin-d7
    Aspirin-d7 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>7</sub>
  • HY-174864
    JP-163-16
    		Inhibitor
    JP-163-16 is a RelA/p65 PROTAC degrader. JP-163-16 selectively reduces the expression of RelA/p65 in a proteasome-dependent manner in cells. JP-163-16 can induce cell apoptosis by inhibiting the NF-κB signaling pathway. JP-163-16 can be used for research on RelA/p65-dependent tumours, such as chronic lymphocytic leukaemia (CLL). (Pink: RelA/p65 Ligand (HY-174865); Blue: CRBN Ligand (HY-A0003); Black: Linker; CRBN Ligand+Linker (HY-160241)).
    JP-163-16
  • HY-P10966
    Tat-IKIP (46-60)
    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-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-172332
    H1L1A1B3
    		Activator
    H1L1A1B3 is an ionizable cationic lipid used in the formation of lipid nanoparticles (LNPs) for the delivery of circular RNA (circRNA). H1L1A1B3-LNPs demonstrates a fourfold increase in circRNA transfection efficiency in lung cancer cells over ALC-0315 (HY-138170). H1L1A1B3 can activate the NF-κB/IRF immune pathways.
    H1L1A1B3
Cat. No. Product Name / Synonyms Application Reactivity
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Download NF-κB Signaling Pathway Map.

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.

NF-κB Isoform Comparison

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