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-147972
    NF-κB/MAPK-IN-1
    Inhibitor 98.71%
    NF-κB/MAPK-IN-1 (compound 11a) is a potent inhibitor of NF-κB and MAPK pathway. NF-κB/MAPK-IN-1 shows inhibitory activity against NO production, with an IC50 of 6.96 µM. NF-κB/MAPK-IN-1 suppresses LPS-induced iNOS, COX-2, ERΚ and P38 signaling activation. NF-κB/MAPK-IN-1 can prevent LPS induced inflammatory response in macrophages. NF-κB/MAPK-IN-1 can be used for rheumatoid arthritis (RA) research.
    NF-κB/MAPK-IN-1
  • HY-N1921
    Edpetiline
    Inhibitor 99.81%
    Edpetiline is an anti-inflammatory agent. Edpetiline inhibits the phosphorylation of IκB, nuclear transcription/translocation of NF-κB p65, as well as the phosphorylation of p38 MAPK and ERK MAPK. Edpetiline reduces intracellular ROS levels, inhibits the expression of TNF-α, IL-6, iNOS, COX-2, and promotes the expression of IL-4. Edpetiline is applicable to the research of diseases associated with inflammation and oxidative stress.
    Edpetiline
  • HY-N0168A
    (Rac)-Hesperetin
    Inhibitor 99.28%
    (Rac)-Hesperetin is the racemate of Hesperetin (HY-N0168), an orally active multi-target inhibitor. (Rac)-Hesperetin exhibits significant anti-tumor and anti-inflammatory activities by blocking the TGF-β1-mediated Fyn/RhoA signaling axis and the TLR4-MyD88-NF-κB inflammatory pathway. (Rac)-Hesperetin inhibits the formation of actin stress fibers and the migration and invasion of cancer cells, and is suitable for triple-negative breast cancer research. In inflammation models, (Rac)-Hesperetin effectively alleviates lung injury by reducing the release of pro-inflammatory mediators and regulating the activity of oxidative stress enzymes, and is suitable for acute lung injury research. (Rac)-Hesperetin also interferes with the entry and early replication processes of channel catfish virus, inhibits viral gene expression and progeny virus production, thereby protecting cells from virus-induced cytopathic effects.
    (Rac)-Hesperetin
  • HY-N6588
    3,4,5-Tricaffeoylquinic acid
    Inhibitor 98.71%
    3,4,5-Tricaffeoylquinic acid (3,4,5-triCQA) inhibits tumor necrosis factor-α-stimulated production of inflammatory mediators in keratinocytes via suppression of Akt- and NF-κB-pathways. 3,4,5-Tricaffeoylquinic acid induces cell cycle arrest at G0/G1, actin cytoskeleton organization, chromatin remodeling, neuronal differentiation, and bone morphogenetic protein signaling in human neural stem cells. 3,4,5-Tricaffeoylquinic acid has the potential for the research of aging-associated diseases.
    3,4,5-Tricaffeoylquinic acid
  • HY-N8307
    Syringaresinol
    Inhibitor 99.66%
    Syringaresinol is a lignan-type phytochemical with anti-inflammatory activities. Syringaresinol inhibits the NF-κB and AKT signaling pathway in IL-1β-activated mouse chondrocytes. Syringaresinol increases phosphorylation of AMPK, eNOS, and intracellular Ca2+ levels in HUVECs. Syringaresinol attenuates osteoarthritis progression in mice with Destabilization of the Medial Meniscus (DMM)-induced osteoarthritis. Syringaresinol can be used for the study of osteoarthritis (OA).
    Syringaresinol
  • HY-N0924
    (±)-Stylopine
    Inhibitor 99.86%
    (±)-Stylopine (Tetrahydrocoptisine) is an alkaloid compound. (±)-Stylopine can be isolated from the tubers of the plant Corydalis. (±)-Stylopine inhibits TNF-α, IL-6, and NO production, and attenuates phosphorylation of p38 MAPK, ERK1/2. (±)-Stylopine inhibits NF-κB expression. (±)-Stylopine exhibits anti-inflammatory activity. (±)-Stylopine has protective effects against foot edema, gastric ulcers, anxiety, depression, and acute lung injury.
    (±)-Stylopine
  • HY-125740
    Malvidin-3-glucoside chloride
    Inhibitor 99.87%
    Malvidin-3-glucoside (Malvidin-3-O-glucoside; Oenin) chloride is an orally active inhibitor of the NF-κB pathway, which blocks inflammatory responses induced by TNF-α, reduces IκB-α degradation and p65 nuclear translocation, and upregulates endothelial nitric oxide synthase eNOS to increase NO production. Malvidin-3-glucoside chloride exerts anti-inflammatory and antioxidant effects by inhibiting pro-inflammatory molecules such as MCP-1, ICAM-1, and IL-6, and regulating intestinal microorganisms and metabolites, while protecting endothelial cells and improving intestinal microecological dysbiosis under inflammatory conditions. Malvidin-3-glucoside chloride can be used to study chronic inflammatory-related diseases such as atherosclerosis and inflammatory bowel disease, and has the potential to prevent vascular inflammation and improve intestinal health.
    Malvidin-3-glucoside chloride
  • HY-148877
    AT-533
    Inhibitor 98.38%
    AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs).
    AT-533
  • HY-90003
    Tianeptine
    Inhibitor 99.84%
    Tianeptine is an atypical antidepressant. Tianeptine is a moderate-intensity agonist of the μ-opioid receptor (MOR), and to a lesser extent, is an agonist of the δ-opioid receptor (DOR). Tianeptine is a glutamate modulator that can enhance AMPA receptor and antagonize NMDA receptor. tianeptine increases sensitivity of the α1 adrenergic receptor, which only manifests in chronic treatment. Tianeptine exerts neuroprotective effects under stress/inflammation-induced conditions, exhibiting anti-inflammatory and antioxidant properties. Tianeptine inhibits MMP-9 by suppressing the PI3K/Akt-mediated NF-κB pathway. Tianeptine can be used to alleviate symptoms of depression and anxiety, but does not cause sedative effects.
    Tianeptine
  • HY-B1640R
    Ethacrynic acid (Standard)
    Inhibitor
    Ethacrynic acid (Standard) is the analytical standard of Ethacrynic acid. This product is intended for research and analytical applications. Ethacrynic acid (Etacrynic acid) is a diuretic. Ethacrynic acid is an inhibitor of glutathione S-transferases (GSTs). Ethacrynic acid is a potent inhibitor of NF-kB-signaling pathway, and also modulates leukotriene formation. Ethacrynic acid also inhibits L-type voltage-dependent and store-operated calcium channel, leading to relaxation of airway smooth muscle (ASM) cells. Ethacrynic acid has anti-inflammatory properties that reduces the retinoid-induced ear edema in mice.
    Ethacrynic acid (Standard)
  • HY-W089835
    Sodium taurodeoxycholate hydrate
    Inhibitor
    Sodium taurodeoxycholate hydrate is a bile salt-related anionic detergent. Sodium taurodeoxycholate hydrate is formed in the liver by conjugation of deoxycholate with Taurine (HY-B0351). Sodium taurodeoxycholate hydrate is used for isolation of membrane proteins including inner mitochondrial membrane proteins. Taurodeoxycholate-d6 (TDCA) exhibits anti-inflammatory and neuroprotective effects.
    Sodium taurodeoxycholate hydrate
  • HY-N0392
    Polygalasaponin F
    Inhibitor 99.85%
    Polygalasaponin F is an orally active triterpenoid saponin monomer. Polygalasaponin F downregulates the expression of Bax, p53, caspase-3, NF-κB p65 and MEK1; restores and upregulates the expression of Bcl-2; activates the PI3K/Akt signaling pathway; inhibits the phosphorylation of p38 MAPK, nuclear translocation of NF-κB, TLR4-mediated signaling pathway, mitophagy (Mitophagy) and ROS production; enhances cell viability and suppresses apoptosis (Apoptosis). Polygalasaponin F maintains mitochondrial function, alleviates Ca2+ overload, upregulates pCREB and BDNF, preserves cell viability and inhibits the release of inflammatory cytokines. Polygalasaponin F alleviates lung injury induced by influenza A H1N1 and cerebral ischemia-reperfusion injury. Polygalasaponin F is applicable to researches related to Parkinson's disease, cerebral ischemia, pneumonia induced by influenza A H1N1, stroke and Alzheimer's disease.
    Polygalasaponin F
  • HY-N7981
    Pratensein
    Inhibitor 99.92%
    Pratensein, a flavonoid, ameliorates β-amyloid-induced cognitive impairment in rats via reducing oxidative damage and restoring synapse and BDNF levels.
    Pratensein
  • HY-N0026
    2'-Acetylacteoside
    Inhibitor 99.73%
    2'-Acetylacteoside (2'-AA) is a natural compound with oral activity and blood-brain barrier permeability. 2'-Acetylacteosideexhibits MAO‑B inhibitory activity (IC50 = 17.71 μM, Ki = 13.81 μM). 2'-Acetylacteoside downregulates the expression of RANK, TRAF6, NF‑κB, NFATc1 and IKKβ, disrupts the RANKL/RANK interaction, blocks downstream signaling pathways, and increases the level of phosphorylated Akt. 2'-Acetylacteoside possesses potent anti-osteoclastogenic, anti-bone resorptive, pro-neurogenic, neuroprotective and antioxidant activities. 2'-Acetylacteoside can be used in the research of osteoporosis, ischemic stroke and Parkinson's disease.
    2'-Acetylacteoside
  • HY-169053
    SU1261
    Inhibitor 99.13%
    SU1261 is an IKK inhibitor with Ki values of 10 nM and 680 nM for IKKα and IKKβ, respectively. SU1261 can inhibit non-canonical NF-κB signaling in U2OS osteosarcoma cells.
    SU1261
  • HY-145532
    S-Allylmercaptocysteine
    Inhibitor
    S-allylmercaptocysteine, an organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. S-allylmercaptocysteine achieves its anti-cancer effect through a variety of pathways such as inducing the apoptosis of cancer cells through the TGF-β signaling pathway, or reducing the NF-κB activity and up-regulating Nrf2 to achieve the effects of anti-inflammation and anti-oxidation.
    S-Allylmercaptocysteine
  • HY-N0726
    Dracorhodin perchlorate
    Inhibitor 99.02%
    Dracorhodin perchlorate (Dracohodin perochlorate) is a natural product that can be obtained from the natural active molecule Dragon's blood. Dracorhodin perchlorate inhibits PI3K/Akt and NF-κB activation, upregulates p53 expression, activates caspase, produces ROS, and promotes Apoptosis. Dracorhodin perchlorate regulates the TLR4. Dracorhodin perchlorate promotes wound healing, improves diabetes. Dracorhodin perchlorate has anti-tumor activity against prostate cancer, breast cancer, cervical cancer and other cancers.
    Dracorhodin perchlorate
  • HY-N1490
    14-Deoxy-11,12-didehydroandrographolide
    Inhibitor 99.93%
    14-Deoxy-11,12-didehydroandrographolide is an analogue of Andrographolide. 14-Deoxy-11,12-didehydroandrographolide inhibits NF-κB activation.
    14-Deoxy-11,12-didehydroandrographolide
  • HY-114519
    Helenalin acetate
    Inhibitor 99.55%
    Helenalin acetate, a natural NF-κB inhibitor, is a potent C/EBPβ inhibitor. Helenalin acetate has anti-inflammatory and anticancer activities.
    Helenalin acetate
  • HY-N1356
    Reticuline
    Inhibitor 98.89%
    Reticuline shows anti-inflammatory effects through JAK2/STAT3 and NF-κB signaling pathways. Reticuline inhibits mRNA expressions of TNF-α, and IL-6 and reduces the phosphorylation levels of JAK2 and STAT3. Reticuline exhibits cardiovascular effects.
    Reticuline
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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