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-N17562
    Acutissimalignan B
    Inhibitor
    Acutissimalignan B is a natural product. Acutissimalignan B can be isolated from Daphne kiusiana var. atrocaulis (Rehd.) F. Maekawa. Acutissimalignan B can reduce the mRNA expression of inflammatory cytokines (iNOS, TNF-α, IL-1β, and IL-6), inhibit the phosphorylation of IκBα, and inhibit the nuclear translocation of NK-κB p65. Acutissimalignan B shows anti-neuroinflammatory effects.
    Acutissimalignan B
  • HY-174419
    TFSeB
    Inhibitor
    TFSeB is an orally active neuroprotective agent. TFSeB can reduce Streptozotocin (STZ) (HY-13753) induced MAO-B and AChE activity. TFSeB exerts neuroprotective effects by increasing the expression of BCL-2, BDNF, NRF2, and decreasing the expression of BAX. TFSeB can reduce lipid peroxidation (TBARS) and reactive oxygen species (ROS) levels. TFSeB can reduce neuroinflammation. TFSeB can be used for research on Alzheimer’s disease.
    TFSeB
  • HY-P10462
    SAP15
    Inhibitor
    SAP15 (Synthetic anti-inflammatory peptide 15) is a synthetic anti-inflammatory peptide consisting of 15 amino acids designed from human beta-defensin 3. SAP15 has the ability to penetrate cells and is able to induce downregulation of intracellular inflammation. SAP15 inhibits inflammation by inhibiting the phosphorylation of HDAC5 and thereby reducing the phosphorylation of NF-κB p65. SAP15 inhibits HDAC5 and NF-κB p65 phosphorylation in LPS (HY-D1056)-induced macrophages. SAP15 increases the expression of aggrecan and type II collagen and decreases the expression of osteocalcin in LPS-induced chondrocytes. SAP15 can be used in the study of inflammation regulation and anti-inflammatory therapy of biomaterials.
    SAP15
  • HY-N7043R
    Isosilybin A (Standard)
    Inhibitor
    Isosilybin A (Standard) is the analytical standard of Isosilybin A (HY-N7043). 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 (Standard)
  • HY-124067
    EC-70124
    Inhibitor
    EC-70124 is an orally active multikinase inhibitor targeting IKKβ and JAK2. EC-70124 blocks IkB phosphorylation and STAT3 (Tyr705) activation, suppressing NF-κB nuclear translocation and STAT3 transcriptional activity. EC-70124 reduces tumor growth and cancer stem cell (CSC) populations in prostate cancer cells and xenograft models. EC-70124 is promising for research of prostate cancer.
    EC-70124
  • HY-106801
    Girolline
    Modulator
    Girolline (RP 49532) is a protein synthesis inhibitor and a functional modulator of eIF5A. Girolline induces ribosome stalling by interfering with the binding of eIF5A to ribosomes. Girolline also inhibits the production of IL-6 and IL-8, and induces cell cycle arrest in tumor cells. Girolline is applicable to research related to inflammatory diseases, solid tumors, leukemia and malaria.
    Girolline
  • HY-N0460R
    1-Caffeoylquinic acid (Standard)
    Inhibitor
    1-Caffeoylquinic acid (Standard) is the analytical standard of 1-Caffeoylquinic acid. This product is intended for research and analytical applications. 1-Caffeoylquinic acid is an effective NF-κB inhibitor, shows significant binding affinity to the RH domain of p105 with Ki of 0.007 μM. 1-Caffeoylquinic acid has anti-oxidative stress ability. 1-Caffeoylquinic acid is the inhibitor for PD-1/PD-L1.
    1-Caffeoylquinic acid (Standard)
  • HY-170585
    COX-2-IN-51
    Inhibitor
    COX-2-IN-51 (E25) is a potent COX-2 inhibitor, with an IC50 of 70.7 nM. COX-2-IN-51 significantly inhibits LPS-induced release of NO and PGE2, expression of COX-2 and iNOS, and activation of NF-κB pathway. COX-2-IN-51 exhibits anti-inflammatory and analgesic effects in diverse murine models through inhibiting NF-κB pathway. COX-2-IN-51 has lower gastrointestinal side effects than Indomethacin (HY-14397).
    COX-2-IN-51
  • HY-178983
    SHP2-IN-45
    Inhibitor
    SHP2-IN-45 (Compound 6) is a potent, highly selective, and orally active SHP2 allosteric inhibitor. SHP2-IN-45 significantly reduces the expressions of IL-6, TNF-α, IL-1β, and iNOS. SHP2-IN-45 inhibits the polarization of M1-type macrophages. SHP2-IN-45 can inhibit the NF-κB pathway. SHP2-IN-45 can be used in the research of sepsis and acute lung injury.
    SHP2-IN-45
  • HY-182236
    JRN73958
    Inhibitor
    JRN73958 (Reduced scytonemin) is a PI3K/Akt, MAPK, and NF-κB inhibitor found in Nostoc commune. JRN73958 inhibits nitric oxide production, induce reactive oxygen species (ROS) generation, and lead to autophagy. JRN73958 decreases LPS (HY-D1056)/IFNγ-induced PI3K/Akt, MAPK, and NF-κB activity. JRN73958 can be used for the research of leukemia.
    JRN73958
  • HY-N0589S
    Dehydrodiisoeugenol-d4
    Inhibitor
    Dehydrodiisoeugenol-d4 is the deuterium labeled Dehydrodiisoeugenol (HY-N0589). Dehydrodiisoeugenol is an orally active anti-inflammatory and anti-tumor agent. Dehydrodiisoeugenol inhibits the proliferation of colorectal cancer cells, and induces apoptosis, autophagy, endoplasmic reticulum stress and cell cycle arrest. Dehydrodiisoeugenol also exerts anti-inflammatory effects by inhibiting the activation of NF-κB and the expression of COX-2. Dehydrodiisoeugenol can be used in the research related to colorectal cancer, inflammatory diseases and ulcerative colitis.
    Dehydrodiisoeugenol-d<sub>4</sub>
  • HY-172619
    BS-153
    Inhibitor
    BS-153 is a novel synthetic oxazolidinone agent with anti-inflammatory activities by blocking the activation of the NF-κB/PKCθ pathway. BS-153 inhibits the expression levels of iNOS and COX-2 and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) on LPS-stimulated RAW264.7 cells.
    BS-153
  • HY-N2497R
    Isoliquiritin apioside (Standard)
    Inhibitor
    Isoliquiritin apioside (Standard) is the analytical standard of Isoliquiritin apioside. This product is intended for research and analytical applications. Isoliquiritin apioside significantly decreases PMA-induced increases in MMP9 activities and suppresses PMA-induced activation of MAPK and NF-κB. Isoliquiritin apioside auppresseses invasiveness and angiogenesis of cancer cells and endothelial cells.
    Isoliquiritin apioside (Standard)
  • HY-184001
    LT-1339-553
    Inhibitor
    LT-1339-553 is a selective, orally active RIPK1 inhibitor with IC50 values of 4.32, 95.74 and 84.33 nM against RIPK1, RIPK2 and RIPK3, respectively. LT-1339-553 exerts anti-necroptotic activity by inhibiting the AKT/PI3K/NF-κB pathway and the IL-17 pathway. LT-1339-553 reduces liver injury, inflammatory responses and collagen deposition. LT-1339-553 can be used in studies related to schistosomiasis-induced liver fibrosis.
    LT-1339-553
  • HY-W705168
    Yangonin-d3
    Yangonin-d3 is the deuterium labeled Yangonin (HY-N0919). Yangonin exhibits affinity for the human recombinant cannabinoid CB1 receptor with an IC50 and a Ki of 1.79 μM and 0.72 μM, respectively.
    Yangonin-d<sub>3</sub>
  • HY-147129
    cGAS-IN-9
    Inhibitor
    cGAS-IN-9 is a cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) inhibitor, with IC50 values of 27.5 nM and 5.15 μM against human and murine cGAS, respectively. cGAS-IN-9 shows weak inhibitory activity against human soluble adenylate cyclase, with an IC50 of 26.4 μM. cGAS-IN-9 inhibits dsDNA-induced expression of IFNB1 and CXCL10, as well as activation of the NF-κB pathway, in human immune cells. cGAS-IN-9 can be used in research related to cGAS-dependent inflammatory diseases.
    cGAS-IN-9
  • HY-N0212R
    Peimine (Standard)
    Inhibitor
    Peimine (Standard) is the analytical standard of Peimine. This product is intended for research and analytical applications. Peimine (Verticine; Dihydroisoimperialine) is an orally active natural product. Peimine has anti-inflammatory, analgesic and cough relieving effects. Peimine can be used in cancer and inflammation related research.
    Peimine (Standard)
  • HY-N0043R
    Ginsenoside Rd (Standard)
    Inhibitor
    Ginsenoside Rd (Standard) is the analytical standard of Ginsenoside Rd. This product is intended for research and analytical applications. Ginsenoside Rd inhibits TNFα-induced NF-κB transcriptional activity with an IC50 of 12.05±0.82 μM in HepG2 cells. Ginsenoside Rd inhibits expression of COX-2 and iNOS mRNA. Ginsenoside Rd also inhibits Ca2+ influx. Ginsenoside Rd inhibits CYP2D6, CYP1A2, CYP3A4, and CYP2C9, with IC50s of 58.0±4.5 μM, 78.4±5.3 μM, 81.7±2.6 μM, and 85.1±9.1 μM, respectively.
    Ginsenoside Rd (Standard)
  • HY-173410
    iNOs-IN-6
    Inhibitor
    iNOs-IN-6 is an anti-inflammatory agent. iNOs-IN-6 inhibits NF-κB, iNOS, and MAPK expression(IC50: 0.2-0.62 μM). iNOs-IN-6 reduces IL-6, TNF-α, and IL-1β pro-inflammatory mediators levels (IC50: 0.4-0.69 μM).
    iNOs-IN-6
  • HY-N15196
    Andrographolide-lipoic acid
    Inhibitor
    Andrographolide-lipoic acid is an Andrographolide (HY-N0191) analogue, which is formed by the coupling of Andrographolide and Lipoic acid (HY-18733). Andrographolide-lipoic acid inhibits NF-κB and has anti-diabetic and β-cell protective activities.
    Andrographolide-lipoic acid
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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