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-N0629R
    Maslinic acid (Standard)
    Inhibitor
    Maslinic acid (Standard) is the analytical standard of Maslinic acid. This product is intended for research and analytical applications. Maslinic acid can inhibit the DNA-binding activity of NF-κB p65 and abolish the phosphorylation of IκB-α, which is required for p65 activation.
    Maslinic acid (Standard)
  • HY-121851
    Revaprazan
    Inhibitor
    Revaprazan (SB 641257) is reversible proton pump inhibitor. Revaprazan can inhibit gastric acid secretion and protect gastric mucosa. Revaprazan can inhibit IkappaB-alpha degradation as well as Akt inactivation, resulting in attenuation of H. pylori-induced COX-2 expression. Revaprazan can be used for the researches of infection and inflammmation, such as H. pylori-infected gastric inflammation and gastric ulcer.
    Revaprazan
  • HY-144745
    HSR1304
    Inhibitor
    HSR1304 (Compound 5d) is a potent inhibitor of NFκB. The multifunctional transcription factor, nuclear factor-κB (NF-κB), is broadly involved in multiple human diseases, such as cancer and chronic inflammation. HSR1304 has the potential for the research of cancer diseases.
    HSR1304
  • HY-14654A
    Aspirin lithium
    Inhibitor
    Aspirin (Acetylsalicylic Acid) lithium is an orally active, potent and irreversible inhibitor of cyclooxygenase COX-1 and COX-2, with IC50 values of 5 and 210 μg/mL, respectively. Aspirin lithium induces apoptosis. Aspirin lithium inhibits the activation of NF-κB. Aspirin lithium also inhibits platelet prostaglandin synthetase, and can prevent coronary artery and cerebrovascular thrombosis.
    Aspirin lithium
  • HY-B0008A
    Sulindac sodium
    Inhibitor
    Sulindac (MK-231) is an orally active nonsteroidal anti-inflammatory agent. Sulindac also is an immunomodulatory agent. Sulindac can be used for the research of arthritis of the spine, gouty arthritis and kinds of cancer including colorectal cancer (CRC) and lung cancer.
    Sulindac sodium
  • HY-183934
    Anti-inflammatory agent 99
    Inhibitor
    Anti-inflammatory agent 99 is a chalcone derivative. Anti-inflammatory agent 99 inhibits LPS (HY-D1056)-induced NF-κB nuclear translocation and suppress the phosphorylation of JNK, ERK, and p38. Anti-inflammatory agent 99 inhibits the expression of cytoinflammatory factors such as TNF-α and IL-6 induced by LPS. Anti-inflammatory agent 99 can be used for the research of LPS-induced septic shock.
    Anti-inflammatory agent 99
  • HY-111165
    SNX-7081
    Inhibitor
    SNX-7081 is an Hsp90 inhibitor with Ki and IC50 values of 26 nM and 44 nM, respectively. SNX-7081 blocks the nuclear translocation of NF-κB, inhibits the production of pro-inflammatory cytokines, attenuates the ERK/JNK and PDGF signaling pathways, and suppresses LPS (HY-D1056)-induced nitric oxide production. SNX-7081 inhibits DNA repair, induces G2/M cell cycle arrest, and triggers apoptosis via downregulation of MYC/nucleolin and activation of Fas. SNX-7081 can be used in research related to rheumatoid arthritis and cancer.
    SNX-7081
  • HY-P11489
    RN-0001
    Inhibitor
    RN-0001 is a cyclophilin (Cyp) inhibitor with Ki values of 4.1 nM and 12.0 nM against CypA and CypD, respectively, and an EC50 of 916 nM for CypD. RN-0001 binds directly to CypD, inhibits the peptidyl-prolyl cis-trans isomerase activities of CypD and CypA, and prevents CypD-dependent mitochondrial permeability transition pore opening. RN-0001 improves mitochondrial function, reduces ROS production, inhibits the expression of lipogenic markers, blocks the nuclear translocation of NF-κB p65, and decreases the release of activated caspase-3 and cytochrome c. RN-0001 can be used in the research of alcohol-associated liver disease.
    RN-0001
  • HY-100507A
    Avadomide hydrochloride
    Inhibitor
    Avadomide hydrochloride (CC 122 hydrochloride) is the hydrochloride form of Avadomide (HY-100507). Avadomide hydrochloride is an orally active cereblon modulator. Avadomide hydrochloride 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 hydrochloride exhibits potent antitumor and immunomodulatory activities.
    Avadomide hydrochloride
  • HY-N0176S
    Dihydroartemisinin-d3
    Inhibitor
    Dihydroartemisinin-d3 is the deuterium labeled Dihydroartemisinin. Dihydroartemisinin is a potent anti-malaria agent.
    Dihydroartemisinin-d<sub>3</sub>
  • HY-170692
    Hypoglycemic agent 3
    Inhibitor
    Hypoglycemic agent 3 (Compound H26), a derivative of corosolic acid, exhibits lipid-lowering and significant hypoglycemic effects and can be used as a hypoglycemic agent. Hypoglycemic agent 3 inhibits insulin resistance by targeting MCCC1 and can be used in the study of type 2 diabetes.
    Hypoglycemic agent 3
  • HY-170579
    Antioxidant agent-20
    Inhibitor
    Antioxidant agent-20 (Compound 3d) has potent anti-inflammatory and antioxidant activity. Antioxidant agent-20 reduces reactive oxygen species (ROS) and apoptosis in a dose-dependent manner. Antioxidant agent-20 exhibits photoprotective effect against UVB-irradiated human skin keratinocytes (HaCaT) (IC50=5.13 µM) via activation of Nrf2/HO-1 signaling and inhibition of NF-κB pathway.
    Antioxidant agent-20
  • HY-W012732R
    Isoquinoline (Standard)
    Inhibitor
    Isoquinoline (Standard) is the analytical standard of Isoquinoline. This product is intended for research and analytical applications. Isoquinoline is an analog of pyridine. Isoquinoline structural-based alkaloids, such as tropoloisoquinoline, phthalideisoquinoline, and naphthylisoquinoline has anti-cancer activities.
    Isoquinoline (Standard)
  • HY-14654B
    Aspirin DL-lysine
    Inhibitor
    Aspirin DL-lysine (ASA DL-lysine) is a lysine-containing aspirin derivative. Aspirin DL-lysine inhibits cyclooxygenase (COX) in platelets, blocks the synthesis of thromboxane A2 (TXA2), and thus inhibits platelet aggregation and activation. Aspirin DL-lysine can be used to study thrombin generation in patients with unstable angina pectoris.
    Aspirin DL-lysine
  • HY-162092
    Multi-target Pt
    Inhibitor
    Multi-target Pt (IV), an antitumor agent, suppresses the IKKβ phosphorylation, IκBα phosphorylation and NF-κB p65 phosphorylation and nuclear translocation, leading to blocked the NF-kB signal pathway.
    Multi-target Pt
  • HY-16362
    Omtriptolide sodium
    Inhibitor
    Omtriptolide sodium (PG490-88Na) is a derivative of Triptolide (HY-32735). Omtriptolide sodium exhibits significant immunosuppressive, anti-fibrotic and anti-inflammatory properties. The mechanism of action of Omtriptolide sodium is diverse, including inhibiting T cell activation and proliferation, inducing T cell apoptosis (apoptosis), blocking fibroblast maturation/proliferation, inhibiting TGF-β mRNA expression, and suppressing pro-inflammatory cytokines (such as IL-2, IFN-γ, TNF-α) by blocking transcription factors such as NF-κB. Omtriptolide sodium can be used for research on obstructive airway diseases, pulmonary fibrosis and graft-versus-host disease.
    Omtriptolide sodium
  • HY-178132
    Apoptosis inducer 46
    Inhibitor
    Apoptosis inducer 46 is an apoptosis inducer. Apoptosis inducer 46 exhibits potent and selective growth inhibitory effects on metastatic triple-negative breast cancer (TNBC) cells. Apoptosis inducer 46 induces G2/M phase cell cycle arrest and apoptotic cell death in MDA-MB-231 cells, and blocks NF-κB nuclear translocation. Apoptosis inducer 46 can be used for the study of TNBC.
    Apoptosis inducer 46
  • HY-B1014S1
    Acenocoumarol-d4
    Inhibitor
    Acenocoumarol-d4 is deuterium labeled Acenocoumarol (HY-B1014). Acenocoumarol is an anticoagulant that functions as a Vitamin K antagonist. Acenocoumarol inhibits MAPK/ERK/JNK signaling pathway, reduces the nuclear translocation of NF-κB p65, activates Akt/GSK3β signaling pathway. Acenocoumarol induces apoptosis in cell A549, arrests cell cycle at S phase.
    Acenocoumarol-d<sub>4</sub>
  • HY-N1333
    Rubioncolin C
    Inhibitor
    Rubioncolin C exerts anti-tumor activity by inducing apoptotic and autophagic Cell Death and inhibiting the NF-κB and Akt/mTOR/P70S6K Pathway in Human Cancer Cells.
    Rubioncolin C
  • HY-N0705R
    Curculigoside (Standard)
    Inhibitor
    Curculigoside (Standard) is the analytical standard of Curculigoside. This product is intended for research and analytical applications. Curculigoside is the main saponin in C. orchioide, exerts significant antioxidant, anti-osteoporosis, antidepressant and neuroprotection effects. Curculigoside possesses significant anti-arthritic effects in vivo and in vitro via regulation of the JAK/STAT/NF-κB signaling pathway.
    Curculigoside (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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