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-N2119R
    Sciadopitysin (Standard)
    Inhibitor
    Sciadopitysin (Standard) is the analytical standard of Sciadopitysin. This product is intended for research and analytical applications. Sciadopitysin is a type of biflavonoids in leaves from ginkgo biloba. Sciadopitysi inhibits RANKL-induced osteoclastogenesis and bone loss by inhibiting NF-κB activation and reducing the expression of c-Fos and NFATc1.
    Sciadopitysin (Standard)
  • HY-N1159
    Teuclatriol
    Inhibitor
    Teuclatriol is an NF-κB inhibitor can be isolated from salvia mirzayanii, has anti-inflammatory effects. Teuclatriol inhibits TNF-α secretion in a dose-dependent manner.
    Teuclatriol
  • HY-100507R
    Avadomide (Standard)
    Inhibitor
    Avadomide (Standard) is the analytical standard of Avadomide. This product is intended for research and analytical applications. Avadomide is an orally active cereblon modulator. Avadomide modulates cereblon E3 ligase activity, inhibits NF-κB pathway, arrests the cell cycle at G1 phase, and thus induces apoptosis in cancer cell PDAC. Avadomide exhibits potent antitumor and immunomodulatory activities.
    Avadomide (Standard)
  • 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-N1445R
    Isoquercitrin (Standard)
    Inhibitor
    Isoquercetin (Standard) is the analytical standard of Isoquercetin. This product is intended for research and analytical applications. Isoquercetin (Quercetin 3-glucoside) is a naturally occurring polyphenol that has antioxidant, anti-proliferative, and anti-inflammatory properties. Isoquercetin alleviates ethanol-induced hepatotoxicity, oxidative stress, and inflammatory responses via the Nrf2/ARE antioxidant signaling pathway. Isoquercetin regulates the expression of nitric oxide synthase 2 (NO2) via modulating the nuclear factor-κB (NF-κB) transcription regulation system. Isoquercetin has high bioavailability and low toxicity, is a promising candidate agent to prevent birth defects in diabetic pregnancies.
    Isoquercitrin (Standard)
  • 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 inhibitor for NF-κB with an IC50 of 85 nM. Bengamide B inhibits LPS (HY-D1056)-induced expression of TNF-α, IL-6 and MCP-1, exhibits anti-inflammatory activity. Bengamide B exhibits antitumor efficacy (IC50 for HCT-116 is 2 nM).
    Bengamide B
  • HY-B0130S1
    Perindopril-d5
    Perindopril-d5 (S-9490-d5) is deuterium labeled Perindopril. Perindopril (S-9490) is an orally available, long-acting angiotensin-converting enzyme (ACE) inhibitor. Perindopril inhibits inflammatory cell influx and intimal thickening, preserving elastin on the inside of the aorta. Perindopril effectively inhibits experimental abdominal aortic aneurysm (AAA) formation in a rat model and reduces pulmonary vasoconstriction in rats with pulmonary hypertension.
    Perindopril-d<sub>5</sub>
  • 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-124508
    Lambertellin
    Activator
    Lambertellin is an effective antibiotic that can be used as a bactericide and as a fungicide. Lambertellin exerts its anti-inflammatory effect in LPS (HY-D1056)-stimulated RAW 264.7 macrophage cells by modulating the activation of the MAPK and NF-κB signaling pathways.
    Lambertellin
  • 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-N15315
    Triptriolide
    Activator
    Triptriolide inhibits Puromycin aminonucleoside PAN (HY-15695)-induced apoptosis in mouse podocytes through regulation of Bcl-2 family proteins and inhibition of Caspase-3. Triptriolide promotes the cell survival, protects and restores the podocyte function through activation of TAK1-NF-κB signaling pathway and upregulation of podocin.
    Triptriolide
  • 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)
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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