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-170659
    NF-κB-IN-18
    Inhibitor
    NF-κB-IN-18 (Compound 5k) is an orally active NF-κB inhibitor. NF-κB-IN-18 inhibits phosphorylation of p65. NF-κB-IN-18 exhibits potent anti-inflammatory activity in Xylene-induced ear edema mice.
    NF-κB-IN-18
  • HY-P992178
    ALLO-647
    ALLO-647 is a human monoclonal antibody targeting CD52. ALLO-647 transiently and selectively depletes host lymphocytes to promote the proliferation of allogeneic CAR T-cell following infusion. ALLO-647 can be used for the research of B-cell lymphoma and follicular lymphoma.
    ALLO-647
  • HY-129724
    α-MSH (11-13)
    Modulator
    α-MSH (11-13) (ACTH-(11-13)) is a C-terminal tripeptide of α-MSH that can cross the blood-brain barrier. α-MSH (11-13) exhibits antipyretic, anti-inflammatory, and antibacterial activities. α-MSH (11-13) also exerts neuroprotective effects after traumatic brain injury by inhibiting excessive activation of microglia and reducing neuronal apoptosis. α-MSH (11-13) can be used in research related to traumatic brain injury, fever, and bacterial infections.
    α-MSH (11-13)
  • HY-163355
    COX-2/15-LOX-IN-5
    Inhibitor
    COX-2/15-LOX-IN-5 (Compound 4f) is a dual inhibitor of COX-2/15-LOX. COX-2/15-LOX-IN-5 attenuates increased NF-κB activation in RAW 264.7 macrophages mediated by lipopolysaccharide (HY-D1056). COX-2/15-LOX-IN-5 has anti-inflammatory and antioxidant activities.
    COX-2/15-LOX-IN-5
  • HY-N0809R
    Sesamolin (Standard)
    Inhibitor
    Sesamolin (Standard) is the analytical standard of Sesamolin. This product is intended for research and analytical applications. Sesamolin, isolated from Sesamum indicum, has antioxidative activity, Sesaminol inhibits lipid peroxidation and shows neuroprotection effect. Sesamolin potently inhibits MAPK cascades by preventing phosphorylation of JNK, p38 MAPKs, and caspase-3 but not ERK-MAPK expression.
    Sesamolin (Standard)
  • HY-P10854
    TAT-N15
    Inhibitor
    TAT-N15 is a p55PIK inhibitor with remarkable anti-inflammatory activity and neuroprotective effects. TAT-N15 can significantly inhibit the activation of IL-6, IL-8, Akt, and NF-κB pathways, as well as suppress the protein expression of phosphorylated STAT3 and NF-κB. By inhibiting the activation of Akt, STAT3, and NF-κB pathways, TAT-N15 is used in research on acute conjunctivitis, allergic rhinitis, chronic obstructive pulmonary disease (COPD), and stroke.
    TAT-N15
  • HY-RS09256
    Nfkb1 Rat Pre-designed siRNA Set A
    Inhibitor

    Nfkb1 Rat Pre-designed siRNA Set A contains three designed siRNAs for Nfkb1 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.

    Nfkb1 Rat Pre-designed siRNA Set A
  • HY-139716
    IMD-catechol
    Modulator
    IMD-catechol is a novel imidazoquinolinone-NF-κB immunomodulator dimer that improves efficacy in a CT26 mouse colon carcinoma tumor model while eliciting minimal adjuvant toxicity.
    IMD-catechol
  • HY-118160
    PPM-18
    Inhibitor 99.17%
    PPM-18 (NSC 73233) is a Vitamin K (HY-B2172) analog. PPM-18 prevents LPS-induced IκBα degradation, thereby inhibiting NF-κB activation and nuclear translocation of NF-κB. PPM-18 inhibits LPS-induced nitrite production and iNOS expression. PPM-18 inhibits HDAC6. PPM-18 induces ROS accumulation, activates AMPK, inhibits the mTORC1 and PI3K/AKT pathways, initiates Autophagy, and induces Apoptosis. PPM-18 suppresses seizures in zebrafish and mouse epilepsy models. PPM-18 prevents LPS-induced lethal toxicity and delayed hypotension. PPM-18 exhibits anticancer activity against leukemia and bladder cancer. PPM-18 can be used in research related to septic shock, bladder cancer and atherosclerosis.
    PPM-18
  • HY-122521
    Sootepin D
    Inhibitor
    Sootepin D (compound 6), a triterpene from the apical bud of Gardenia sootepensis, inhibits TNF-α-induced NF-κB activity with an IC50 of 8.3μM. Sootepin D has anti-inflammatory activity.
    Sootepin D
  • HY-P10469
    NBD-2
    Inhibitor
    NBD-2 is an inhibitor of the NEMO-IKKα/β interaction in the NF-κB signaling pathway. NBD-2 specifically inhibits the typical NF-κB signaling pathway in vitro and in vivo, reducing the inflammatory response in lipopolysaccharide (LPS) induced acute lung injury (ALI). NBD-2 exhibits significant anti-inflammatory activity. NBD-2 can be used to study diseases related to NF-κB signaling pathway, including autoimmune diseases, cancer, etc.
    NBD-2
  • HY-N9980
    Antcin K
    Inhibitor
    Antcin K is a selective inhibitor targeting the PI3K/Akt, NF-κB, MEK1/2-ERK, p38 and AP-1 pathways. Antcin K upregulates IL-10 expression, thereby inhibiting the production of pro-inflammatory factors, blocking monocyte adhesion, reducing tissue damage, and promoting myogenesis. Antcin K has significant anti-inflammatory, anti-damage and tissue protective activities. Antcin K is mainly used in the research of inflammation-related diseases such as periodontitis, rheumatoid arthritis, and skeletal muscle injury.
    Antcin K
  • HY-N0716BR
    Berberine sulfate (Standard)
    Inhibitor
    Berberine (sulfate) (Standard) is the analytical standard of Berberine (sulfate). This product is intended for research and analytical applications. Berberine sulfate is an alkaloid isolated from the Chinese herbal medicine Huanglian, as an antibiotic. Berberine sulfate induces reactive oxygen species (ROS) generation and inhibits DNA topoisomerase. Berberine sulfate has antineoplastic properties. The sulfate form improves bioavailability[1][2].
    Berberine sulfate (Standard)
  • HY-P992321
    BAY-356
    Activator
    BAY-356, a potent TWEAK receptor agonist, is an aglycosylated anti-TWEAK receptor antibody. BAY-356 triggers TWEAKR hyperactivation, activates NFκB and STAT1 pathways, and undergoes TWEAKR-dependent internalization. BAY-356 can be used for the research of colorectal cancer, bladder cancer, non-small cell lung cancer and pancreatic cancer[1][2].
    BAY-356
  • HY-183586
    G721-0377
    Inhibitor
    G721-0377 is a CHI3L1 modulator with a human Kd value of 45 μM. G721-0377 binds to CHI3L1 and modulates downstream signaling pathways. G721-0377 suppresses CHI3L1-induced NF-κB activation, decreases secretion of CHI3L1 and IL-6. G721-0377 can be used for the research of Alzheimer's disease.
    G721-0377
  • HY-P992399
    LBL-019
    Activator
    LBL-019 is a humanized IgG1 monoclonal antibody targeting TNFR2. LBL-019 costimulates TNFR2 and activates the NF-κB signaling pathway in an Fc crosslinking-dependent manner. LBL-019 can be used for the research of advanced malignant tumors, including hepatocellular carcinoma and melanoma. The recommended isotype control is human IgG1 kappa (HY-P99001).
    LBL-019
  • HY-181132
    dCASP1-55
    Activator
    dCASP1-55 is a cereblon-dependent caspase-1 (CASP1) PROTAC degrader. dCASP1-55 induces excessive NF-κB activation, apoptosis, and moderate S-phase arrest in leukemic cells. dCASP1-55 suppresses colony formation of leukemic cells. dCASP1-55 can be used for the research of cancer, such as myeloid malignancies and acute myeloid leukemia.
    dCASP1-55
  • HY-180120
    UM-203
    Inhibitor
    UM-203 is a reversible covalent STING antagonist. UM-203 is effective against both mouse and human STING, and in particular, it inhibits the most common human STING R232 variant. UM-203 can inhibit STING oligomerization and reduce phosphorylation of downstream TBK1 and IRF3, thereby blocking the IRF3 and NF-κB-mediated signaling pathways and inhibiting IFNβ and IL-6 secretion. UM-203 can be used for the research of inflammation and immunology, such as systemic lupus erythematosus.
    UM-203
  • HY-184157
    IB15C
    Inhibitor
    IB15C is an ILT3 (LILRB4) inhibitor with a human Kd of 0.92 μM. IB15C binds to a specific ILT3 pocket, disrupts ApoE interaction, and interferes with downstream inhibitory signaling pathways. IB15C reduces SHP1 and SHP2 phosphorylation, suppresses pro-inflammatory cytokine secretion, enhances amyloid uptake, and attenuates NF-κB activation. IB15C can be used for the research of alzheimer's disease.
    IB15C
  • HY-172088
    Tubulin/MMP-IN-3
    Inhibitor
    Tubulin/MMP-IN-3 (Compound 15j) is the dual inhibitor for tubulin polymerization and MMP, and inhibits MMP-2 and MMP-9 with IC50 of 21.13 μM and 19.24 μM. Tubulin/MMP-IN-3 inhibits NF-κB signaling pathway, causes mitochondrial dysfunction and the apoptosis through a mitochondrial-dependent pathway. Tubulin/MMP-IN-3 exhibits antiproliferative activity in a variety of cancer cells, arrests the cell cycle at G2/M phase, and exhibits antitumor efficacy in mouse models.
    Tubulin/MMP-IN-3
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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