1. シグナル伝達
  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.

製品番号 製品名 製品効果 純度 構造式
  • HY-U00450R
    4-O-Methyl honokiol (Standard) Inhibitor
    4-O-Methyl honokiol is a natural neolignan isolated from Magnolia officinalis, acts as a PPARγ agonist, and inhibtis NF-κB activity, used for cancer and inflammation research.
    4-O-Methyl honokiol (Standard)
  • HY-N12283
    NF-κB-IN-13 Inhibitor
    NF-κB-IN-13 (compound 12) can significantly inhibit LPS-induced NF-κB activation and NO production in RAW264.7 macrophages. NF-κB-IN-13 has anti-inflammatory effects.
    NF-κB-IN-13
  • HY-13812R
    QNZ (Standard) Inhibitor
    QNZ (Standard) is the analytical standard of QNZ. This product is intended for research and analytical applications. QNZ (EVP4593) shows strong inhibitory effects on NF-κB transcriptional activation and TNF-α production with IC50s of 11 and 7 nM, respectively. QNZ (EVP4593) is a neuroprotective inhibitor of SOC channel.
    QNZ (Standard)
  • HY-N0721R
    Neoandrographolide (Standard) Inhibitor
    Neoandrographolide (Standard) is the analytical standard of Neoandrographolide. This product is intended for research and analytical applications. Neoandrographolide is a diterpenoid compound isolated from Andrographis paniculata. Neoandrographolide inhibits osteoclasts differentiation and bone resorption through inhibition of MAPK/NF-κB/PI3K/AKT/GSK3β/PPAR/CAMK signaling pathway. Neoandrographolide inhibits apoptosis in rat embryonic ventricular cardiomyocytes. Neoandrographolide inhibits iNOS and the generation of ROS, activates eNOS, exhibiting anti-inflammatory and hypolipidemic activity.
    Neoandrographolide (Standard)
  • HY-135317C
    Emavusertib tosylate Inhibitor
    Emavusertib tosylate (CA-4948 tosylate) is the tosylate salt form of Emavusertib (HY-135317). Emavusertib tosylate is an orally active inhibitor for IRAK4 (IC50=57 nM) and FLT3. Emavusertib tosylate inhibits NF-κB and MyD88 signaling pathways, reduces the generation of pro-inflammatory cytokines like IL-6 and IL-10, thereby exhibiting anti-inflammatory and anti-proliferative activities against cancer cells, leading to cell apoptosis. Emavusertib tosylate exhibits antitumor activity in mouse model.
    Emavusertib tosylate
  • HY-116035R
    Nimbolide (Standard) Inhibitor
    Nimbolide (Standard) is the analytical standard of Nimbolide. This product is intended for research and analytical applications. Nimbolide is a triterpene compound that can be isolated from neem (Azadirachta indica), possesses anticancer and antiproliferative activity. Nimbolide induces tumor cell apoptosis by inhibiting NF-κB and CDK4/CDK6 kinase. Nimbolide suppresses the Wnt, PI3K-Akt, MAPK and JAK-STAT signaling pathways.
    Nimbolide (Standard)
  • HY-110151
    Bengamide B Inhibitor
    Bengamide B is an alkaloid with anti-tumor and anti-inflammatory activities. Bengamide B reduces the phosphorylation level of IκBα, thereby blocking the activation of NF-κB. Bengamide B inhibits the proliferation of tumor cells. Bengamide B can be used in research related to inflammatory diseases and cancers.
    Bengamide B
  • HY-N4150R
    Quercetagitrin (Standard) Inhibitor
    Quercetagitrin (Standard) is the analytical standard of Quercetagitrin. This product is intended for research and analytical applications. Quercetagitrin (Quercetagetin-7-O-glucoside) is a natural product that can be isolated from the African marigold (Tagetes erecta). Quercetagitrin has anti-inflammatory activity. Quercetagitrin inhibits Tau accumulation. Quercetagitrin can reverse neuroinflammation and cognitive deficits in P301S-Tau transgenic mouse model through inhibiting NF-κB activation. Quercetagitrin is a dual-target inhibitor of PTPN6 (IC50 = 1 μM) and PTPN9 (IC50 = 1.7 μM). Quercetagitrin enhances glucose uptake by mature C2C12 myoblasts. Quercetagitrin can be studied in research for Alzheimer’s disease and type 2 diabetes.
    Quercetagitrin (Standard)
  • HY-15027S3
    5-Aminosalicylic acid-d3 disodium Inhibitor
    5-Aminosalicylic acid-d3 disodium is deuterated labeled 5-Aminosalicylic Acid (HY-15027). 5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB.5-Aminosalicylic acid can inhibit the activity of osteopontin (OPN).
    5-Aminosalicylic acid-d<sub>3</sub> disodium
  • HY-N2056R
    11-Keto-beta-boswellic acid (Standard) Inhibitor
    11-Keto-beta-boswellic acid (Standard) is the analytical standard of 11-?Keto-?beta-?boswellic acid. This product is intended for research and analytical applications. 11-Keto-beta-boswellic acid (11-Keto-β-boswellic acid) is a pentacyclic triterpenic acid of the oleogum resin from the bark of the Boswellia serrate tree, popularly known as Indian Frankincense. 11-Keto-beta-boswellic acid has the anti-inflammatory activity is primarily due to inhibit 5-lipoxygenase (5-LOX) and subsequent leukotriene and nuclear factor-kappa B (NF-κB) activation and tumor necrosis factor alpha generation production.
    11-Keto-beta-boswellic acid (Standard)
  • HY-168090
    Anti-osteoporosis agent-11 Inhibitor
    Anti-osteoporosis agent-11 (compound 3k) is an anti-osteoporosis compound targeting osteoclasts. Anti-osteoporosis agent-11 has the most significant inhibitory effect on osteoclast differentiation, with an IC50 value of 0.36 μM. In addition, Anti-osteoporosis agent-11 inhibits osteoclast formation, bone resorption, and the expression of osteoclast-specific genes by blocking rankl-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.
    Anti-osteoporosis agent-11
  • HY-N0696R
    Sipeimine (Standard) Inhibitor
    Sipeimine (Standard) is the analytical standard of Sipeimine (HY-N0696R). Sipeimine (Imperialine) is an inhibitor targeting the PI3K/AKT/NF-κB pathway and NLRP3 inflammasome, which can competitively bind to PI3K and p65. Sipeimine inhibits PI3K/AKT phosphorylation, blocks NF-κB nuclear translocation and NLRP3 inflammasome activation. Sipeimine exerts anti-inflammatory activities, inhibits pyroptosis and ferroptosis, and protects the extracellular matrix. Sipeimine can reduce cartilage degradation and synovial inflammation in osteoarthritis and improve PM2.5-induced lung injury. Sipeimine is mainly used in the study of anti-inflammatory and degenerative diseases.
    Sipeimine (Standard)
  • HY-17403R
    Manidipine dihydrochloride (Standard) Inhibitor
    Manidipine (dihydrochloride) (Standard) is the analytical standard of Manidipine (dihydrochloride). This product is intended for research and analytical applications. Manidipine dihydrochloride is a third-generation, lipophilic, orally active and highly vasoselective calcium channel antagonist (IC50 = 2.6 nM in guinea-pig ventricular cells) and acts as an antihypertensive agent. Manidipine effectively reduces blood pressure as well as improving insulin sensitivity, renal protection, and antiatherosclerotic activity. Manidipine also exerts anti-inflammatory activity mediated by NF-κB and antiviral activity against many flavivirus and negative-strand RNA viruses through the inhibition of calcium channel. Manidipine is widely applied to research of cardiovascular, metabolic disease and infection.
    Manidipine dihydrochloride (Standard)
  • HY-N2609R
    7,4'-Dihydroxyflavone (Standard) Inhibitor
    7,4'-Dihydroxyflavone (7,4'-DHF) is a flavonoid, which can be isolated from Glycyrrhiza uralensis. 7,4'-Dihydroxyflavone is eotaxin/CCL11 inhibitor and CBR1 inhibitor (IC50=0.28 μM). 7,4'-Dihydroxyflavone has the ability to consistently suppress eotaxin production and prevent dexamethasone (Dex)‐paradoxical adverse effects on eotaxin production. 7,4'-Dihydroxyflavone (7,4'-DHF) inhibits MUC5AC gene expression, mucus production and secretion via regulation of NF-κB, STAT6 and HDAC2.7,4'-Dihydroxyflavone (7,4'-DHF) decreases phorbol 12-myristate 13-acetate (PMA) stimulated NCI-H292 human airway epithelial cell MUC5AC gene expression and mucus production with IC50 value of 1.4 µM.
    7,4'-Dihydroxyflavone (Standard)
  • HY-N0143R
    Phlorizin (Standard) Inhibitor
    Phlorizin (Floridzin) (Standard) is the analytical standard of Phlorizin. This product is intended for research and analytical applications. Phlorizin is an orally active non-selective sodium-glucose cotransporter (SGLT) inhibitor, with an IC50 of 0.04 μM and a Ki of 39 nM against hSGLT2, and an IC50 of 0.17 μM and a Ki of 0.31 μM against hSGLT1. Phlorizin promotes GLUT4 translocation, inhibits gluconeogenesis and promotes glycogen synthesis by activating the PI3K/Akt/mTOR pathway. Phlorizin reduces DNA damage and apoptosis (apoptosis) by inhibiting the NF-κB inflammatory pathway. Phlorizin induces apoptosis via activating the Caspase pathway by antagonizing the JAK/STAT3 and PCK pathways. Phlorizin also exhibits antibacterial, anti-inflammatory and neuroprotective activities.
    Phlorizin (Standard)
  • HY-W011849R
    Phenyl β-D-glucopyranoside (Standard) Inhibitor
    Phenyl β-D-glucopyranoside (Standard) is the analytical standard of Phenyl β-D-glucopyranoside (HY-W011849). This product is intended for research and analytical applications. Phenyl β-D-glucopyranoside is a component isolated from Phellodendron amurense, which has anti-inflammatory and anti-tumor activities. Phenyl β-D-glucopyranoside inhibits nitric oxide (NO) production, and the expression of iNOS and COX-2. Phenyl β-D-glucopyranoside also inhibits the nuclear translocation of NF-κB. Phenyl β-D-glucopyranoside inhibits the expression of pro-inflammatory cytokines and related genes.
    Phenyl β-D-glucopyranoside (Standard)
  • HY-P990252
    Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2) Inhibitor
    Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2) is an anti-mouse Delta-like protein 4/DLL4 IgG monoclonal antibody. Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2) can reduce angiogenesis and density by blocking the DLL4-Notch signaling pathway. Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2) reduces inflammatory response by decreasing NF-κB activity and pro-inflammatory factors (IL-1β, iNOS, IL-6) levels. Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2) can inhibit Th17 cell differentiation and IL-17A production. Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2) can reduce macrophage infiltration and alleviate insulin resistance. Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2) can be used for researches on inflammation, metabolic conditions and cancer such as atherosclerosis, pancreatic cancer and asthma.
    Anti-Mouse Delta-like protein 4/DLL4 Antibody (HMD4-2)
  • HY-B1104R
    Indoprofen (Standard) Inhibitor
    Indoprofen (Standard) is the analytical standard of Indoprofen. This product is intended for research and analytical applications. Indoprofen activates AKT-AMPK signaling pathway, inhibits NF-κB/MAPK signaling pathway. Indoprofen exhibits anti-inflammatory and immunomodulatory activities. Indoprofen is orally active.
    Indoprofen (Standard)
  • HY-N0803S1
    Myrcene-13C3 Inhibitor
    Myrcene-13C3 is 13C labeled Myrcene (HY-N0803). Myrcene (β-Myrcene) is a type of aromatic compound that inhibits TNFα and NF-κB activity. Myrcene has anti-invasive action, inhibits cell cycle, and leads to cancer cell apoptosis. Myrcene has strong blood protection effect, anti-inflammation, and anti-inflammatory activity.
    Myrcene-<sup>13</sup>C<sub>3</sub>
  • HY-N0493R
    Pectolinarigenin (Standard) Inhibitor
    Pectolinarigenin (Standard) is the analytical standard of Pectolinarigenin. This product is intended for research and analytical applications. Pectolinarigenin is an orally active dual inhibitor of COX-2/5-LOX with anti-inflammatory, antioxidant, antitumor and neuroprotective activities. Pectolinarigenin exerts neuroprotective and anti-inflammatory effects on astrocyte inflammation via the NFκB and MAPK pathways. Pectolinarigenin inhibits LPS-induced phosphorylation of ERK1/2, N-FκB and p38MAPK, directly inhibits the enzymatic activity or binding of COX-2, 5-LOX and HIF-1α, and reduces the level of XIAP. Pectolinarigenin modifies Keap1 to promote nuclear accumulation of Nrf2, induces ARE-mediated antioxidant enzyme expression, and possesses direct free radical scavenging activity. Pectolinarigenin reduces the release of NO, proinflammatory mediators and leukotrienes, and increases the level of IL-10. Pectolinarigenin induces G2/M cell cycle arrest, apoptosis (Apoptosis) and autophagy (Autophagy) via the PI3K/AKT/mTOR signaling pathway. Pectolinarigenin reduces renal crystal deposition and inhibits melanin synthesis. Pectolinarigenin inhibits inflammation and alleviates allergy in mouse models of inflammation. Pectolinarigenin alleviates renal injury, inflammation and oxidative stress in mice by inhibiting HIF-1α activity. Pectolinarigenin can be used for the research of neurodegenerative diseases, inflammatory/allergic diseases, calcium oxalate nephrocalcinosis, gastric cancer, melasma, post-inflammatory diseases and chloasma.
    Pectolinarigenin (Standard)
製品番号 製品名 / 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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