2. Signaling Pathways
  3. NF-κB
  4. NF-κB

NF-κB

Nuclear factor-κB; Nuclear factor-kappaB

NF-κB

Related Products

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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.

NF-κB Isoform Specific Products:

NF-κB Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-W001023A
    5-Amino-8-hydroxyquinoline dihydrochloride
    		Inhibitor
    5-Amino-8-hydroxyquinoline (5A8HQ; 5AHQ) dihydrochloride is an orally active non-competitive 20S proteasome inhibitor. 5-Amino-8-hydroxyquinoline dihydrochloride can inhibit NF-κB activity and induce cancer cells death and shows low cytotoxicity towards normal hematopoietic cells. 5-Amino-8-hydroxyquinoline dihydrochloride can be used for the research of cancer, such as leukemia.
    5-Amino-8-hydroxyquinoline dihydrochloride
  • HY-N0735R
    Phellodendrine chloride (Standard)
    		Inhibitor
    Phellodendrine chloride (Standard) is the analytical standard of Phellodendrine chloride (HY-N0735). Phellodendrine chloride is an orally active plant alkaloid. Phellodendrine chloride inhibits the proliferation of KRAS-mutated pancreatic cancer cells by suppressing macropinocytosis and glutamine metabolism, inducing ROS accumulation and mitochondrial apoptosis. Phellodendrine chloride promotes autophagy by activating the AMPK/mTOR pathway, alleviating intestinal damage in ulcerative colitis. Phellodendrine chloride can alleviate gouty arthritis by inhibiting the IL-6/STAT3 signaling pathway. Phellodendrine chloride suppresses allergic reactions by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequent downstream MAPK and NF-κB signaling. Phellodendrine chloride inhibits the AKT/NF-κB pathway and down-regulates the expression of COX-2, thereby protecting zebrafish embryos from oxidative stress. Phellodendrine chloride has an anti-major depressive disorder (MDD) effect by down-regulating CHRM1, HTR1A, and the PI3K/Akt signaling pathway.
    Phellodendrine chloride (Standard)
  • HY-172409
    CB1R antagonist 2
    		Inhibitor
    CB1R antagonist 2 (Compound 11g) is the antagonist for cannabinoid receptor 1 (CB1R), that inhibits MAPK/NF-κB signaling pathway and exhibits anti-inflammatory activity. CB1R antagonist 2 inhibits LPS (HY-D1056)-induced IL-6, IL-1β and TNF-α expressions in RAW264.7. CB1R antagonist 2 ameliorates OVA-induced allergic rhinitis in mouse models.
    CB1R antagonist 2
  • HY-158156
    NF-κB-IN-16
    		Inhibitor
    NF-κB-IN-16 (compound 9) is a complex (Pt(IV) complex) of NF-κB inhibitor and Cisplatin (HY-17394), which has high efficacy and low toxicity in anti-tumor activity. active. NF-κB-IN-16 can cause DNA damage, induce mitochondrial dysfunction, produce reactive oxygen species, and induce apoptosis through the mitochondrial pathway and endoplasmic reticulum stress. NF-κB-IN-16 potently inhibits the NF-κB/MAPK signaling pathway and disrupts PI3K/AKT signaling. NF-κB-IN-16 also exhibits excellent in vivo antitumor efficiency and low toxicity in A549 or A549/CDDP xenograft models.
    NF-κB-IN-16
  • HY-N2423B
    (E/Z)-Sinigrin free base
    		Inhibitor
    (E/Z)-Sinigrin ((E/Z)-Allyl-glucosinolate; (E/Z)-2-Propenyl-glucosinolate) free base is an orally active aliphatic thioglucoside anti-leukemia compound. Allyl isothiocyanate, produced by the hydrolysis of (E/Z)-sinigrin free base by myrosinase, has an IC50 of 2.71 μM against HL60 leukemia cells. The hydrolysis products of (E/Z)-sinigrin free base can further activate apoptosis pathways, inhibit NF-κB and MAPK signaling pathways, and induce phase II metabolic enzyme activity, thus exhibiting anti-cancer, anti-inflammatory, antibacterial, antioxidant, and wound healing activities. (E/Z)-Sinigrin free base can be used in research on cancer, inflammation-related diseases (such as atherosclerosis), and infectious diseases. (E/Z)-Sinigrin free base can be naturally extracted from the seeds of Brassica nigra, Brassica juncea, and other Brassicaceae plants such as broccoli and Brussels sprouts. Methyl pechueloate is a guaiane-type sesquiterpene ester compound and a potential precursor of xerantholide. It is useful in the structural elucidation and biosynthetic pathway studies of sesquiterpenoids. Methyl pechueloate can be naturally extracted from the aerial parts of Pechuel-Loeschea leibnitziae (Kuntze) O. Hoffm.
    (E/Z)-Sinigrin free base
  • HY-B0516AR
    Articaine (Standard)
    		Inhibitor
    Articaine (Standard) is the analytical standard of Articaine (HY-B0516A). This product is intended for research and analytical applications. Articaine (Hoe-045) hydrochloride is a selective inhibitor of voltage-gated sodium channels (such as rNav1.4, hNav1.7, and rNav1.8), with an IC50 of 15.8 μM for open-state Na+ channels, and IC50 of 40.6 μM and 378 μM for inactivated and resting-state Na+ channels, respectively. Articaine hydrochloride exerts local anesthetic activity by inhibiting Na+ influx to block nerve impulse conduction, and can also inhibit NF-κB activation and NLRP3 inflammasome pathways, exhibiting anti-inflammatory function. Articaine hydrochloride can be used in the study of dental local anesthesia and inflammatory-related diseases (such as acute kidney injury).
    Articaine (Standard)
  • HY-180899
    CHI3L1-IN-5
    		Inhibitor 98.60%
    CHI3L1-IN-5 (Compound Z17) is a highly selective CHI3L1 inhibitor with a KD value of 6 μM. CHI3L1-IN-5 restores the clearance ability of astrocytes by rejuvenating lysosomal function and Aβ uptake. CHI3L1-IN-5 alleviates neuroinflammation by inhibiting the NF-κB pathway. CHI3L1-IN-5 can be used for research on Alzheimer's disease.
    CHI3L1-IN-5
  • HY-N0755R
    Rhoifolin (Standard)
    		Activator
    Rhoifolin (Standard) is the analytical standard of Rhoifolin. This product is intended for research and analytical applications. Rhoifolin is a flavone glycoside can be isolated from Rhus succedanea. Rhoifolin has anti-diabetic effect acting through enhanced adiponectin secretion, tyrosine phosphorylation of insulin receptor-β and glucose transporter 4 (GLUT 4) translocation. Rhoifolin has an anti-inflammatory action via multi-level regulation of inflammatory mediators. Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-κB and MAPK pathways. Rhoifolin also has cytotoxic activity against different cancer cell lines.
    Rhoifolin (Standard)
  • HY-155820
    Anti-inflammatory agent 54
    		Inhibitor
    Anti-inflammatory agent 54 (compound 9c) is a derivative of Coixol and has anti-inflammatory activity. Anti-inflammatory agent 54 inhibits the NF-κB pathway and downregulates the expression of iNOS, TNF-α, IL-6 and IL-1β. Anti-inflammatory agent 54 inhibits LPS-induced nitric oxide (NO) production in RAW264.7 macrophages (IC50: 2.4 μM) and exerts in vivo anti-inflammatory activity in a mouse auricular edema model.
    Anti-inflammatory agent 54
  • HY-W011474S
    Geranylgeraniol-d5
    Geranylgeraniol-d5 is the deuterium labeled Geranylgeraniol (HY-W011474). Geranylgeraniol is an orally acitve vitamin K2 sub-type, an intermediate of the mevalonate pathway. Geranylgeraniol targets NF-kB signaling pathway and could alleviate LPS-induced microglial inflammation in animal model.
    Geranylgeraniol-d<sub>5</sub>
  • HY-W709448
    Oxaprozin-d10
    Oxaprozin-d10 (Oxaprozinum-d10; Wy21743-d10) is the deuterium labeled Oxaprozin (HY-B0808). Oxaprozin is an orally active and potent COX inhibitor, with IC50 values of 2.2 μM for human platelet COX-1 and and 36 μM for IL-1-stimulated human synovial cell COX-2, respectively. Oxaprozin also inhibits the activation of NF-κB. Oxaprozin induces cell apoptosis. Oxaprozin shows anti-inflammatory activity. Oxaprozin-mediated inhibition of the Akt/IKK/NF-κB pathway contributes to its anti-inflammatory properties.
    Oxaprozin-d10
  • HY-P5762A
    Phoenixin-14 TFA
    		Inhibitor
    Phoenixin-14 (PNX-14) TFA is an endogenous neuropeptide with multiple biological activities, and serves as the endogenous ligand of GPR173. Phoenixin-14 TFA reduces ROS production by inhibiting the HMGB1/TLR4/MyD88/NF-κB signaling axis, thereby exerting antioxidant and mitochondrial protective effects. Phoenixin-14 TFA inhibits FOXO3 phosphorylation by upregulating SIRT3 expression, suppresses apoptosis, and improves myocardial systolic/diastolic function. Phoenixin-14 TFA resists ferroptosis by activating the ATF4/SLC7A11/GPX4 axis; it activates ERK1/2 phosphorylation via GPR173. Phoenixin-14 TFA can be used in researches on neuroprotection, diabetes, cardiomyopathy, reproductive protection and so on.
    Phoenixin-14 TFA
  • HY-146058
    NF-κB/PON1-IN-1
    		Inhibitor
    NF-κB/PON1-IN-1 (Compound 16) is a NF-κB/PON1 pathway inhibitor. NF-κB/PON1-IN-1 has antioxidant (IC50 = 45.76 µM) and hepatoprotective activities.
    NF-κB/PON1-IN-1
  • HY-W800535
    Cryptolepine
    		Inhibitor
    Cryptolepine is an orally active multi-potent alkaloid with anti-cancer, anti-bacterial, anti-viral, anti-malarial, anti-inflammatory, anti-hyperglycemic, relieve pain and other properties. Cryptolepine acts as an inhibitor of c-Myc, mTOR, NF-κB, HIF-1, MAPK and an activator of AMPKα1/2. It intercalates into DNA, inhibits topoisomerase II (Top II), disrupts mitochondrial dynamics and induces apoptosis. Cryptolepine also exhibits anti-plasmodial and cholinesterase inhibitory activities. Cryptolepine can be used in research related to tumors (melanoma, hepatocellular carcinoma, mammary adenocarcinoma, etc.), malaria, inflammatory diseases and diabetes, particularly in studies focused on inhibiting tumor growth and anti-plasmodial infection.
    Cryptolepine
  • HY-Y0148R
    10-Hydroxydecanoic acid (Standard)
    		Inhibitor
    10-Hydroxydecanoic acid (Standard) is the analytical standard of 10-Hydroxydecanoic acid. This product is intended for research and analytical applications. 10-Hydroxydecanoic acid (10-HDAA) is a saturated fatty acid derived from 10-hydroxy-trans-2-decenoic acid, which can be isolated from royal jelly. 10-Hydroxydecanoic acid exhibits various biological activities, including anti-inflammatory, insecticidal, anti-malarial, and anti-Leishmania properties, as well as enhancing antigen-specific immune responses. The anti-inflammatory effects of 10-Hydroxydecanoic acid are primarily mediated by inhibiting the activation of NF-κB and the translation of interferon regulatory factor 1 (IRF-1), which reduces the production of interleukin 6 (IL-6) and nitric oxide (NO) in inflammatory cells. Additionally, 10-Hydroxydecanoic acid alleviates neuroinflammatory responses through the p53-autophagy pathway and the p53-NLRP3 pathway. Finally, 10-Hydroxydecanoic acid enhances antigen-specific immune responses by promoting the effective uptake of antigens by microfold cells[1][2][3][4][5].
    10-Hydroxydecanoic acid (Standard)
  • HY-17473R
    Embelin (Standard)
    		Inhibitor
    Embelin (Standard) is the analytical standard of Embelin. This product is intended for research and analytical applications. Embelin (Embelic acid), a potent, nonpeptidic XIAP inhibitor (IC50=4.1 μM), inhibits cell growth, induces apoptosis, and activates caspase-9 in prostate cancer cells with high levels of XIAP. Embelin blocks NF-kappaB signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Embelin also induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells.
    Embelin (Standard)
  • HY-W008829
    N,N-Diethylacetamide
    		Inhibitor 99.68%
    N,N-Diethylacetamide is a polar solvent widely used in film and fiber manufacturing, as well as in laboratories as a carrier for water-insoluble chemicals. N,N-Diethylacetamide exerts potent anti-inflammatory effects by inhibiting the NF-κB pathway, suppressing the expression of NO and iNOS, and downregulating key inflammatory cytokines such as TNF-α and IL-6, without affecting the MAPK pathway. N,N-Diethylacetamide can be used to study inflammatory preterm birth.
    N,N-Diethylacetamide
  • HY-N0103R
    Sophocarpine (Standard)
    		Inhibitor
    Sophocarpine (Standard) is the analytical standard of Sophocarpine (HY-N0103). This product is intended for research and analytical applications. Sophocarpine is a PTEN activator and an inhibitor of PI3K/Akt, MEK/ERK, and NF-κB signaling pathways. Sophocarpine upregulates PTEN expression and inhibits PI3K/Akt phosphorylation, arrests tumor cell cycle and induces apoptosis. Sophocarpine inhibits MEK/ERK phosphorylation and VEGF secretion, reducing tumor cell migration. Sophocarpine can also inhibit NF-κB activation and p38 and JNK phosphorylation, reduce the expression of inflammatory factors such as iNOS and COX-2, and activate the Nrf2/HO-1 pathway to reduce oxidative stress. Sophocarpine has anti-tumor, anti-inflammatory, antioxidant and anti-apoptotic effects, and can be used in the research of cancers such as glioblastoma and colorectal cancer, inflammation-related diseases, and Doxorubicin (HY-15142A)-induced cardiac damage.
    Sophocarpine (Standard)
  • HY-P5522
    TriDAP
    		Activator
    TriDAP (L-Ala-γ-D-Glu-meso-diaminopimelic acid) is a NOD1 agonist with a Kd value of 34.5 μM. TriDAP enhances the binding of NOD1-RICK, promotes RICK phosphorylation, and activates the NF-κB, TAK1, MEK/ERK, p38 and interferon response pathways. TriDAP downregulates Runx2 via increasing ubiquitination and reduces trabecular bone parameters. TriDAP decreases IκBα levels and increases p65 levels. TriDAP induces the secretion of proinflammatory mediators IL-8 and prostaglandins, triggers tissue inflammation and innate immune activation, and inhibits SARS-CoV-2 replication in lung epithelial cells. TriDAP increases the RANKL/OPG ratio in mice, reduces bone mass and enhances osteoclast activity, and inhibits new bone formation by decreasing the mineralization deposition rate in mice. TriDAP can be used in research related to pulpitis, chronic ulcerative colitis, Crohn's disease and SARS-CoV-2 infection.
    TriDAP
  • HY-130237R
    Cinnamtannin B-1 (Standard)
    		Inhibitor
    Cinnamtannin B-1 (Standard) is the analytical standard of Cinnamtannin B-1. This product is intended for research and analytical applications. Cinnamtannin B-1 is a anthocyanidin. Cinnamtannin B-1 inhibits the osteoclast formation by inhibiting NF-kB signaling pathway and ROS generation. Cinnamtannin B-1 exhibits antioxidant, anti-inflammatory, antitumor and anti-platelet aggregation activities. Cinnamtannin B-1 is orally active.
    Cinnamtannin B-1 (Standard)
Cat. No. Product Name / Synonyms Application Reactivity
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Download NF-κB Signaling Pathway Map.

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.

NF-κB Isoform Comparison

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