2. Signaling Pathways
  3. Apoptosis
  4. TNF Receptor

TNF Receptor

Tumor Necrosis Factor Receptor; TNFR

TNF Receptor

Related Products

PDF 0.47 MB

Tumor necrosis factor (TNF) is a major mediator of apoptosis as well as inflammation and immunity, and it has been implicated in the pathogenesis of a wide spectrum of human diseases, including sepsis, diabetes, cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases.

TNF-α is a 17-kDa protein consisting of 157 amino acids that is a homotrimer in solution. In humans, the gene is mapped to chromosome 6. Its bioactivity is mainly regulated by soluble TNF-α–binding receptors. TNF-α is mainly produced by activated macrophages, T lymphocytes, and natural killer cells. Lower expression is known for a variety of other cells, including fibroblasts, smooth muscle cells, and tumor cells. In cells, TNF-α is synthesized as pro-TNF (26 kDa), which is membrane-bound and is released upon cleavage of its pro domain by TNF-converting enzyme (TACE).

Many of the TNF-induced cellular responses are mediated by either one of the two TNF receptors, TNF-R1 and TNF-R2, both of which belong to the TNF receptor super-family. In response to TNF treatment, the transcription factor NF-κB and MAP kinases, including ERK, p38 and JNK, are activated in most types of cells and, in some cases, apoptosis or necrosis could also be induced. However, induction of apoptosis or necrosis is mainly achieved through TNFR1, which is also known as a death receptor. Activation of the NF-κB and MAPKs plays an important role in the induction of many cytokines and immune-regulatory proteins and is pivotal for many inflammatory responses.

TNF Receptor Isoform Specific Products:

TNF Receptor Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-N9445
    Lacto-N-neotetraose
    		99.71%
    Lacto-N-neotetraose (LNnT) is an endogenous metabolite. Lacto-N-neotetraose can inhibit TNF-α induced IL-8 secretion in immature epithelial cells. Lacto-N-neotetraose has anti-inflammatory avtivity, and can improve the wound closure.
    Lacto-N-neotetraose
  • HY-148552
    Anti-inflammatory agent 35
    		Inhibitor 99.77%
    Anti-inflammatory agent 35 (compound 5a27) is an orally active curcumin analogue with anti-inflammatory activity. Anti-inflammatory agent 35 blocks mitogen-activated protein kinase (MAPK) signaling and p65 nuclear translocation of NF-kB. Anti-inflammatory agent 35 also inhibits yellow neutrophil infiltration and pro-inflammatory cytokine production. Anti-inflammatory agent 35 significantly attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vivo.
    Anti-inflammatory agent 35
  • HY-100176
    PF-4878691
    		99.89%
    PF-4878691 (3M-852A) is an orally active TLR7 agonist. PF-4878691 has the innate immune response activity, antiviral efficacy against HCV, and can be used for the research of cancer.
    PF-4878691
  • HY-133807A
    (Rac)-Benpyrine
    		Inhibitor 99.30%
    (Rac)-Benpyrine, a racemate of Benpyrine, is a potent and orally active TNF-α inhibitor. (Rac)-Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research.
    (Rac)-Benpyrine
  • HY-122663
    (Rac)-BIO8898
    		Inhibitor 99.81%
    (Rac)-BIO8898 is a CD40-CD154 co-stimulatory interaction inhibitor. (Rac)-BIO8898 inhibits CD154 binding to CD40-Ig with an IC50 of 25 μM.
    (Rac)-BIO8898
  • HY-155751
    HMGB1-IN-1
    		Inhibitor 99.37%
    HMGB1-IN-1 (compound 6) displays strong NO inhibitory effect in RAW264.7 cells with IC50 value of 15.9 ± 0.6 μM. HMGB1-IN-1 inhibit the HMGB1/NF-κB/NLRP3 pathway. HMGB1-IN-1 shows good anti-inflammatory activity and good anti-sepsis effects in kidney injury.
    HMGB1-IN-1
  • HY-13743
    Roquinimex
    		Inhibitor 99.69%
    Roquinimex (Linomide; PNU212616; ABR212616) is a quinoline derivative immunostimulant which increases NK cell activity and macrophage cytotoxicity; inhibits angiogenesis and reduces the secretion of TNF alpha.
    Roquinimex
  • HY-P99315
    Ruplizumab
    		Inhibitor 99.84%
    Ruplizumab (BG 9588) is a humanized monoclonal anti-CD40L (TNF Receptor) IgG1κ antibody. Ruplizumab has the potential for systemic lupus erythematosus disease research.
    Ruplizumab
  • HY-P99220
    Tabalumab
    		Inhibitor 98.11%
    Tabalumab (LY2127399) is a human anti-BAFF (B-cell activating factor) monoclonal antibody (IgG4 type) with neutralising activity against membrane bound and soluble BAFF. Tabalumab can be used in studies of autoimmune diseases such as rheumatoid arthritis, renal failure and systemic lupus erythematosus.
    Tabalumab
  • HY-115620
    AQX-016A
    		Inhibitor 98.00%
    AQX-016A is an orally active and potent SHIP1 agonist. AQX-016A can activate recombinant SHIP1 enzyme in vitro and stimulate SHIP1 activity. AQX-016A also can inhibit the PI3K pathway and TNFa production, can be useful for various inflammatory diseases research.
    AQX-016A
  • HY-111326A
    Naphazoline nitrate
    		Inhibitor ≥98.0%
    Naphazoline (Naphthazoline) nitrate is an α-adrenergic receptor agonist. Naphazoline nitrate reduces vascular hyperpermeability and promotes vasoconstriction. Naphazoline nitrate reduces the levels of inflammatory factors (TNF-α, IL-1β and IL-6), cytokines (IFN-γ and IL-4), IgE, GMCSF, and NGF. Naphazoline nitrate can be used for non-bacterial conjunctivitis research.
    Naphazoline nitrate
  • HY-N9315
    Episappanol
    		Inhibitor 98.57%
    Episappanol is a natural compound isolated from Caesalpinia sappan heartwood with anti-inflammatory activity. Episappanol significantly inhibits the IL-6 and TNF-α secretion.
    Episappanol
  • HY-N1940
    β-Anhydroicaritin
    		Inhibitor 99.09%
    β-Anhydroicaritin is isolated from Boswellia carterii Birdware, has important biological and pharmacological effects, such as antiosteoporosis, estrogen regulation and antitumor properties. β-Anhydroicaritin ameliorates the degradation of periodontal tissue and inhibits the synthesis and secretion of TNF-α and MMP-3 in diabetic rats. β-Anhydroicaritin decreases the overproduction of NO, IL-10, TNF-α, MCP-1 and IL-6 in inperitonitis mice. β-Anhydroicaritin inhibits the elevation of intracellular Ca2+, and markedly decreases iNOS protein expression.
    β-Anhydroicaritin
  • HY-145498
    HDMAPP triammonium
    		Activator
    HDMAPP triammonium is a potent phosphoantigen in the ammonium form and the pyrophosphate form of (E)-HDMAPP. HDMAPP is also a potent activator of γδ T cells and can induce T cell stimulation in vitro (EC50=0.39 nM, TNF-α).
    HDMAPP triammonium
  • HY-P99663
    Inezetamab
    		Inhibitor
    Inezetamab is a bispecific anti-CD40 and anti-MSLN IgG1 monoclonal antibody.
    Inezetamab
  • HY-N2468
    Xylobiose
    		≥98.0%
    Xylobiose (1,4-β-D-Xylobiose; 1,4-D-Xylobiose) is a disaccharide of xylose monomers with a β-1, 4 bond between monomers.
    Xylobiose
  • HY-P99119
    Anti-Mouse 4-1BB/CD137 Antibody (3H3)
    		Inhibitor
    Anti-Mouse 4-1BB/CD137 Antibody (3H3) is an anti-mouse 4-1BB IgG2a antibody inhibitor derived from the host Rat.
    Anti-Mouse 4-1BB/CD137 Antibody (3H3)
  • HY-P99701
    Letolizumab
    		Inhibitor
    Letolizumab (BMS-986004) is a monoclonal antibody targeting CD40L, which is produced to express mutant IgG1 lacking effector function, including Fc binding and complement fixation. Letolizumab reduces rejection, thromboembolism and prolongs the survival time.
    Letolizumab
  • HY-P99361
    Enavatuzumab
    		Inhibitor
    Enavatuzumab (PDL192; ABT-361) is a humanized IgG1 monoclonal antibody targeting the receptor of TNF-like weak inducer of apoptosis (TWEAK). TWEAK (Fn14; TNFRSF12A), the natural ligand of the TWEAK receptor (TweakR), stimulates multiple cellular responses. Enavatuzumab induces tumor growth inhibition through direct TweakR signaling and antibody dependent cell-mediated cytotoxicity (ADCC). Enavatuzumab can actively recruits and activates myeloid effectors to kill tumor cells. Enavatuzumab inhibits the growth of various human TweakR-positive cancer cell lines and xenografts in vitro and in vivo .
    Enavatuzumab
  • HY-B0809R
    Theophylline (Standard)
    		Inhibitor 99.99%
    Theophylline (Standard) is the analytical standard of Theophylline. This product is intended for research and analytical applications. Theophylline (1,3-Dimethylxanthine) is a potent phosphodiesterase (PDE) inhibitor, adenosine receptor antagonist, and histone deacetylase (HDAC) activator. Theophylline (1,3-Dimethylxanthine) inhibits PDE3 activity to relax airway smooth muscle. Theophylline (1,3-Dimethylxanthine) has anti-inflammatory activity by increase IL-10 and inhibit NF-κB into the nucleus. Theophylline (1,3-Dimethylxanthine) induces apoptosis. Theophylline (1,3-Dimethylxanthine) can be used for asthma and chronic obstructive pulmonary disease (COPD) research.
    Theophylline (Standard)
Cat. No. Product Name / Synonyms Species Source
Cat. No. Product Name / Synonyms Application Reactivity
All Rights Reserved.
Download TNF Receptor Signaling Pathway Map.

Following the binding of TNF to TNF receptors, TNFR1 binds to TRADD, which recruits RIPK1, TRAF2/5 and cIAP1/2 to form TNFR1 signaling complex I; TNFR2 binds to TRAF1/2 directly to recruit cIAP1/2. Both cIAP1 and cIAP2 are E3 ubiquitin ligases that add K63 linked polyubiquitin chains to RIPK1 and other components of the signaling complex. The ubiquitin ligase activity of the cIAPs is needed to recruit the LUBAC, which adds M1 linked linear polyubiquitin chains to RIPK1. K63 polyubiquitylated RIPK1 recruits TAB2, TAB3 and TAK1, which activate signaling mediated by JNK and p38, as well as the IκB kinase complex. The IKK complex then activates NF-κB signaling, which leads to the transcription of anti-apoptotic factors-such as FLIP and Bcl-XL-that promote cell survival. 

 

The formation of TNFR1 complex IIa and complex IIb depends on non-ubiquitylated RIPK1. For the formation of complex IIa, ubiquitylated RIPK1 in complex I is deubiquitylated by CYLD. This deubiquitylated RIPK1 dissociates from the membrane-bound complex and moves into the cytosol, where it interacts with TRADD, FADD, Pro-caspase 8 and FLIPL to form complex IIa. By contrast, complex IIb is formed when the RIPK1 in complex I is not ubiquitylated owing to conditions that have resulted in the depletion of cIAPs, which normally ubiquitylate RIPK1. This non-ubiquitylated RIPK1 dissociates from complex I, moves into the cytosol, and assembles with FADD, Pro-caspase 8, FLIPL and RIPK3 (but not TRADD) to form complex IIb. For either complex IIa or complex IIb to prevent necroptosis, both RIPK1 and RIPK3 must be inactivated by the cleavage activity of the Pro-caspase 8-FLIPL heterodimer or fully activated caspase 8. The Pro-caspase 8 homodimer generates active Caspase 8, which is released from complex IIa and complex IIb. This active Caspase 8 then carries out cleavage reactions to activate downstream executioner caspases and thus induce classical apoptosis. 

 

Formation of the complex IIc (necrosome) is initiated either by RIPK1 deubiquitylation mediated by CYLD or by RIPK1 non-ubiquitylation due to depletion of cIAPs, similar to complex IIa and complex IIb formation. RIPK1 recruits numerous RIPK3 molecules. They come together to form amyloid microfilaments called necrosomes. Activated RIPK3 phosphorylates and recruits MLKL, eventually leading to the formation of a supramolecular protein complex at the plasma membrane and necroptosis [1][2].

 

Reference:
[1]. Brenner D, et al. Regulation of tumour necrosis factor signalling: live or let die.Nat Rev Immunol. 2015 Jun;15(6):362-74. 
[2]. Conrad M, et al. Regulated necrosis: disease relevance and therapeutic opportunities.Nat Rev Drug Discov. 2016 May;15(5):348-66. 
 

TNF Receptor Isoform Comparison

Your Search Returned No Results.

Sorry. There is currently no product that acts on isoform together.

Please try each isoform separately.