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-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
  • HY-N0608S
    Myrislignan-13C,d2
    Myrislignan-13C,d2 is the 13C-labeled and deuterium labeled Myrislignan (HY-N0608). Myrislignan, a lignan, possesses anti-inflammatory activities. Myrislignan attenuates LPS-induced inflammation reaction in murine macrophage cells through inhibition of NF-kB signalling pathway activation.
    Myrislignan-<sup>13</sup>C,d<sub>2</sub>
  • 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-N1380S4
    Guaiacol-d4-1
    Guaiacol-d4-1 is the deuterium labeled Guaiacol. Guaiacol, a phenolic compound, inhibits LPS-stimulated COX-2 expression and NF-κB activation. Anti-inflammatory activity.
    Guaiacol-d<sub>4</sub>-1
  • 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
    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
  • HY-175293
    SMU-C68
    Activator
    SMU-C68 is a highly selective small-molecule TLR1/2 heterodimer agonist (EC50=0.009 μM). SMU-C68 activates NF-κB and MAPK pathways to promote pro-inflammatory cytokine release (e.g., TNF-α, IL-1β). SMU-C68 is promising for research of cancers.
    SMU-C68
  • HY-N8816
    Stipuleanoside R2
    Stipuleanoside R2 inhibits NF-κB activation stimulated by TNFα in a dose-dependent manner with IC50 value of 4.1 μM.
    Stipuleanoside R2
  • HY-174865
    MMH-165-26
    Inhibitor
    MMH-165-26 is a ligand for RelA/p65. MMH-165-26 reduces the expression of RelA/p65 and has significant cytotoxicity in MEC-1 (LC50 = 0.37 μM) cells. MMH-165-26 can be used for synthesizing PROTACs such as JP-163-16 (HY-174864).
    MMH-165-26
  • HY-162850
    DOR agonist 2
    Inhibitor
    DOR agonist 2 (Compound 3) is a Delta Opioid Receptor agonist. DOR agonist 2 can inhibit the expression of TNF-α, prevent NF-κB transport to the nucleus, and activate the G protein-mediated ERK1/2 pathway. DOR agonist 2 can be used in the study of neurodegenerative diseases.
    DOR agonist 2
  • HY-P991528
    PE0116
    Activator
    PE0116 is a fully human CD137 agonistic monoclonal antibody generated from immunized harbor H2L2 human transgenic mice. PE0116 is a ligand block. PE0116 activates NF-κB signaling which significantly promotes T-cell proliferation and increases cytokine secretion in vitro. PE0116 exhibits robust antitumor activity in MC38 tumor model.
    PE0116
  • HY-W041489R
    Chelidonic acid (Standard)
    Inhibitor
    Chelidonic acid (Standard) is the analytical standard of Chelidonic acid. This product is intended for research and analytical applications. Chelidonic acid is a component of Chelidonium majus L., used as an antimicrobial. Chelidonic acid also shows anti-inflammatory activity. Chelidonic acid has potential to inhibit IL-6 production by blocking NF-κB and caspase-1. Chelidonic acid is a glutamate decarboxylase inhibitor, with a Ki of 1.2 μM.
    Chelidonic acid (Standard)
  • HY-B0185AS1
    Lidocaine-d6 hydrochloride
    Inhibitor
    Lidocaine-d6 (hydrochloride) is deuterium labeled Lidocaine (hydrochloride). Lidocaine hydrochloride (Lignocaine hydrochloride) inhibits sodium channels involving complex voltage and using dependence. Lidocaine hydrochloride decreases growth, migration and invasion of gastric carcinoma cells via up-regulating miR-145 expression and further inactivation of MEK/ERK and NF-κB signaling pathways. Lidocaine hydrochloride is an amide derivative and a agent to treat ventricular arrhythmia and an effective tumor-inhibitor.
    Lidocaine-d<sub>6</sub> hydrochloride
  • HY-N0633R
    Muscone (Standard)
    Inhibitor
    Muscone (Standard) is the analytical standard of Muscone. This product is intended for research and analytical applications. Muscone is the main active monomer of traditional Chinese medicine musk. Muscone inhibits NF-κB and NLRP3 inflammasome activation. Muscone remarkably decreases the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), and ultimately improves cardiac function and survival rate.
    Muscone (Standard)
  • HY-173221
    MJ210
    Modulator
    MJ210 is a modulator of the NF-κB and MAPK pathways with oral activity and the ability to penetrate the blood-brain barrier, and it exhibits neuroprotective activity. In vitro, 5 μM of MJ210 can increase the survival rate of SH-SY5Y cells treated with Rotenone (HY-B1756) to 81.9% and reduce the level of ROS, etc. In vivo, 5 mg/kg of MJ210 can improve the motor impairment in a rat model of Parkinson's disease. MJ210 can be used in the research of neurological diseases, such as Parkinson's disease.
    MJ210
  • HY-N2534R
    Karanjin (Standard)
    Inhibitor
    Karanjin (Standard) is the analytical standard of Karanjin. This product is intended for research and analytical applications. Karanjin is an orally active furanoflavonoid which can be isolated from several Leguminosae. Karanjin exhibits evident anti-diabetic, anti-cancer, anti-inflammatory, antioxidant, anticolitis, anti-ulcer, anti-Alzheimer properties and multiple insect repellent/insecticidal, acaricide properties, suggesting the potential of Karanjin to be applied to relevant research.
    Karanjin (Standard)
  • HY-N0515R
    Ophiopogonin D (Standard)
    Inhibitor
    Ophiopogonin D (Standard) is the analytical standard of Ophiopogonin D. This product is intended for research and analytical applications. Ophiopogonin D can be isolated from the tubers of Ophiopogon japonicus, is a rare naturally occurring C29 steroidal glycoside. Ophiopogonin D is a CYP2J3 inducer that significantly inhibits Ang II induced NF-κB nuclear translocation, IκBα down-regulation, intracellular Ca2+ overload and activation of pro-inflammatory cytokines by increasing the expression of CYP2J2/EETs and PPARα in human umbilical vein endothelial cells (HUVECs). Ophiopogonin D can inhibit isteoclastic differentiation in RAW264.7 cells. Ophiopogonin D has protective effect as an antioxidant in H2O2-induced endothelial injury. Ophiopogonin D blocks ERK signaling cascades. Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice. Ophiopogonin D has been used against inflammatory, metabolic and cardiovascular diseases.
    Ophiopogonin D (Standard)
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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