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-P99579
    Tamtuvetmab
    Inhibitor
    Tamtuvetmab (AT-005) is a caninised blontuvetmab against CD52. Tamtuvetmab increases progression-free survival (PFS), exhibits in vivo efficacy in dogs with naïve T-cell lymphoma (LSA). Tamtuvetmab has been approved by veterinary.
    Tamtuvetmab
  • HY-176192
    SMU-14a
    Inhibitor
    SMU-14a is a selective Toll-like receptor 3 (TLR3) inhibitor wirh an IC50 of 0.18 μM. SMU-14a reduces phosphorylation of p65, ERK, and TBK1 via NF-κB, MAPK, and IRF3 signaling pathways. SMU-14a inhibits IL-6 secretion in mouse peritoneal macrophages, downregulates TNF-α in human peripheral blood monocytes and decreases serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. SMU-14a can be used for the research of acute hepatitis.
    SMU-14a
  • HY-178041
    BRD4-BD1/2-IN-3
    Inhibitor 99.52%
    BRD4-BD1/2-IN-3 (Compound B6) is a selective BRD4 BD2 inhibitor with an IC50 of 0.41  nM for BRD4 BD2 over BRD4 BD1. BRD4-BD1/2-IN-3 significantly inhibits the LPS (HY-D1056)-induced expression of IL-6. BRD4-BD1/2-IN-3 shows anti-inflammatory activities by modulating the TNF and NF-κB signaling pathway. BRD4-BD1/2-IN-3 can be used for inflammatory diseases research.
    BRD4-BD1/2-IN-3
  • HY-107665
    Ro 106-9920
    Inhibitor ≥99.0%
    Ro 106-9920 is a potent inhibitor of NF-kappaB. Ro 106-9920 has the potential for the research of tumor and cancer diseases.
    Ro 106-9920
  • HY-N1965
    Gaultherin
    Inhibitor 99.44%
    Gaultherin is an orally active non-steroidal anti-inflammatory agent. Gaultherin selectively inhibits NF-κB, MAPK, COX-2 (IC50 = 0.35 mg/mL), LOX (IC50 = 0.56 mg/mL) and HYAL (IC50 = 28.58 μg/mL) to exert anti-inflammatory, antipyretic and analgesic effects. Gaultherin exhibits modest direct antioxidant capacity, greater in cell-based models. Gaultherin does not affect COX-1 so that avoids the common gastrointestinal side effects of Aspirin (HY-14654).
    Gaultherin
  • HY-135808
    BIZ 114
    Inhibitor 98.0%
    BIZ 114 (Example 11) is a fatty acid derivative and potent inhibits the TNF-α activated NF-κΒ pathway. BIZ 114 has the potential to prevent and / or treat ophthalmic disorders such as retinal degenerative disorders and ocular inflammatory diseases.
    BIZ 114
  • HY-B0185G
    Lidocaine (GMP)
    Inhibitor
    Lidocaine (GMP) is Lidocaine (HY-B0185) produced by using GMP guidelines. GMP small molecules work appropriately as an auxiliary reagent for cell therapy manufacture. Lidocaine inhibits sodium channels involving complex voltage and using dependence. Lidocaine decreases growth, migration and invasion of gastric carcinoma cells via up-regulating miR-145 expression and further inactivation of MEK/ERK and NF-κB signaling pathways. Lidocaine is an amide derivative and has potential for the research of ventricular arrhythmia.
    Lidocaine (GMP)
  • HY-N11011
    Withaphysalin A
    Inhibitor 98%
    Withaphysalin A is a withanolide compound with anti-inflammatory and antioxidant activities. Withaphysalin A inhibits LPS (HY-D1056)-induced nuclear translocation of NF-κB p65, as well as phosphorylation of STAT3, ERK, JNK and p38 MAPK. Withaphysalin A upregulates the expression of HO-1. Withaphysalin A inhibits LPS-induced production of NO, PGE2, IL-1β, IL-6 and TNF-α. Withaphysalin A downregulates LPS-induced expression of iNOS and COX-2. Withaphysalin A interacts with B-cell activating factor protein (BAFF) to exert inhibitory effects. Withaphysalin A exhibits ELOVL6 inhibitory activity. Withaphysalin A can be used in the research of inflammatory diseases, nephrotic syndrome and chronic myeloid leukemia.
    Withaphysalin A
  • HY-W012349
    2′-Hydroxychalcone
    Inhibitor
    2′-Hydroxychalcone is a hydroxyl derivative of chalcones with anticancer activities. 2'-Hydroxychalcone inhibits NF-κB pathway and induces autophagy and apoptosis in breast cancer cells. 2′-Hydroxychalcone shows a better antifungal activity against the complex Paracoccidioides spp.
    2′-Hydroxychalcone
  • HY-B1773AS5
    Sodium propionate-d3
    Inhibitor 98.38%
    Sodium propionate-d3 is the deuterium labeled Propionate sodium (HY-B1773A). Sodium propionate is an orally active short-chain fatty acid. Sodium propionate can be produced by intestinal bacteria from the metabolism of dietary fiber. Sodium propionate increases PPAR-γ, inhibits NF-κB activation, and reduces COX-2 expression and NO production. Sodium propionate also induces Apoptosis and Autophagy. Sodium propionate reduces HSV-1-induced keratitis. Sodium propionate has anticancer effects against glioblastoma. Sodium propionate exhibits neuroprotective, antioxidant, and anti-inflammatory activities. Sodium propionate can be used in the research of spinal cord injury and Alzheimer's disease.
    Sodium propionate-d<sub>3</sub>
  • HY-141582S
    Ceramide 3-d3
    Inhibitor 98.0%
    Ceramide 3-d3 (N-Stearoyl phytosphingosine-d3) is deuterium labeled Ceramide 3. Ceramide 3 is an orally active major component of intercellular lipids in the stratum corneum of the skin, and belongs to the ceramide family. Ceramide 3 inhibits c-jun and NF-κB activation induced by Histamine (HY-B1204), and suppresses the expression of IL-4 and TNF-α. Ceramide 3 inhibits scratching behavior and vascular permeability in mice, and exhibits antihistamine effects in guinea pig ileum. Ceramide 3 improves skin barrier function, reduces transepidermal water loss, erythema and the number of circulating epidermal cells, and accelerates barrier repair of irritated or dysfunctional skin.
    Ceramide 3-d<sub>3</sub>
  • HY-N2149R
    Tomatidine (Standard)
    Inhibitor
    Tomatidine acts as an anti-inflammatory agent by blocking NF-κB and JNK signaling. Tomatidine activates autophagy either in mammal cells or C elegans.
    Tomatidine (Standard)
  • HY-13010S
    Laquinimod-d5
    Inhibitor 98.25%
    Laquinimod-d5 (ABR-215062-d5) is deuterium labeled Laquinimod. Laquinimod (ABR-215062), an orally available carboxamide derivative, is a potent immunomodulator that prevents neurodegeneration and inflammation in the central nervous system. Laquinimod reduces astrocytic NF-κB activation to protect from Cuprizone-induced demyelination. Laquinimod has the potential for relapsing-remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases research.
    Laquinimod-d<sub>5</sub>
  • HY-N9454
    Garcinoic acid
    Inhibitor
    Garcinoic acid is an orally active anti-inflammatory agent that crosses the blood-brain barrier. Garcinoic acid also enhances efferocytosis and enzyme/receptor regulation, and selectively inhibits human COX-2, porcine α-amylase, Saccharomyces cerevisiae α-glucosidase and human DNA polymerase β (IC50=11 μM), as well as activates human PXR. Garcinoic acid enhances macrophage efferocytosis via receptors such as MerTK and LRP-1, and promotes the production of pro-resolving lipid mediators. Garcinoic acid inhibits NF-κB activation and pro-inflammatory cytokine secretion, interferes with aggregation, downregulates NLRP3 inflammasome activity, and binds to targets including CD44 and EGFR to inhibit leukemia cell proliferation. The pharmacological activities of Garcinoic acid, such as antioxidant, anti-inflammatory and lipid metabolism-regulating effects, are widely used in studies related to various diseases including atherosclerosis, Alzheimer's disease, type 2 diabetes, inflammatory bowel disease and viral pneumonia.
    Garcinoic acid
  • HY-N0274R
    Caffeic acid phenethyl ester (Standard)
    Inhibitor
    Caffeic acid phenethyl ester (Standard) is the analytical standard of Caffeic acid phenethyl ester. This product is intended for research and analytical applications. Caffeic acid phenethyl ester is a NF-κB inhibitor.
    Caffeic acid phenethyl ester (Standard)
  • HY-W478741
    Pyrraline
    Inhibitor 99.61%
    Pyrraline is an Nrf2 pathway activator with antioxidant and anti-inflammatory effects. Pyrraline upregulates antioxidant enzymes such as NAD(P)H dehydrogenase (NQO1) and heme oxygenase-1 (HO-1) via antioxidant response element (ARE) activation, while inhibiting NFκB-mediated inflammation. Pyrraline is promising for research of metabolic disorders (such as diabetic nephropathy) and cancers.
    Pyrraline
  • HY-N12087
    8-Deoxylactucin
    Inhibitor
    8-Deoxylactucin is an orally active sesquiterpene lactone. 8-Deoxylactucin inhibits LPS (HY-D1056)-induced NO production in RAW264.7 macrophages with an IC50 value of 4.35 μM. 8-Deoxylactucin exerts anti-inflammatory effects by blocking the NF-κB pathway. 8-Deoxylactucin demonstrates hepatoprotective efficacy in LPS/D-galactosamine-induced acute hepatitis model of mice. 8-Deoxylactucin can be used for the study of inflammatory diseases and inflammatory liver injuries.
    8-Deoxylactucin
  • HY-N2543R
    Damascenone (Standard)
    Inhibitor
    Damascenone (Standard) is the analytical standard of Damascenone. This product is intended for research and analytical applications. Damascenone ((E/Z)-Damascenone) is an active compound of Epipremnum pinnatum with anti-inflammatory activity. Damascenone is a mixture complex of E-isomer-Damascenone and Z-isomer Damascenone.
    Damascenone (Standard)
  • HY-N0334
    (+)-Magnoflorine
    Inhibitor
    (+)-Magnoflorine (α-Magnoflorine) is an orally active aporphine alkaloid with multiple biological activities. (+)-Magnoflorine promotes Parkin/PINK1 -mediated mitochondrial autophagy, inhibits the activation of NLRP3/Caspase-1 pathway, regulates the intestinal microbiota, and exhibits significant anti-inflammatory and immunomodulatory activities. (+)-Magnoflorine inhibits JNK and TLR4/NF-κB signaling pathways, activates Sirt1/AMPK pathway, alleviates neuronal oxidative stress and apoptosis. Magnoflorine upregulates miR-410-3p, inhibits HMGB1/NF-κB pathway, and has anti-tumor activity. (+)-Magnoflorine also has significant antifungal activity.
    (+)-Magnoflorine
  • HY-152169
    BIHC
    Inhibitor ≥98.0%
    BIHC is a TNF blocker with anti-inflammatory activity. BIHC can significantly inhibit the proliferation of hepatocellular carcinoma (HCC) cells and exhibits potent cytotoxicity against the HepG2 cell line, capable of inducing cell apoptosis , while demonstrating relatively low toxicity towards normal hepatocytes. Additionally, BIHC can be used for research on inflammatory bowel disease (IBD).
    BIHC
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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