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-106359A
    Delmitide acetate
    		Inhibitor 98.55%
    Delmitide (RDP58) acetate is an orally active d-isomer decapeptide with potent anti-inflammatory activity. Delmitide acetate inhibits production of TNF-α, IFN-γ, and interleukin (IL)-12, and up-regulates heme oxygenase 1 activity. Delmitide acetate can be used for the research of ulcerative colitis.
    Delmitide acetate
  • HY-N6927
    Isoforskolin
    		Inhibitor ≥98.0%
    Isoforskolin is the principle active component of C. forskohlii native to China. Isoforskolin reduces the secretion of lipopolysaccharide (LPS)-induced cytokines, namely TNF-α, IL-1β, IL-6 and IL-8, in human mononuclear leukocytes. Isoforskolin acts as an anti-inflammatory agent for the treatment of Lyme arthritis.
    Isoforskolin
  • HY-N8593
    Undecane
    		Inhibitor 99.66%
    Undecane has anti-allergic and anti-inflammatory activities on sensitized rat basophilic leukemia (RBL-2H3) mast cells and HaCaT keratinocytes. In sensitized mast cells, Undecane inhibits degranulation and the secretion of histamine and TNF-α[
    Undecane
  • HY-N1940
    β-Anhydroicaritin
    		Inhibitor 99.69%
    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-114095
    BML-280
    		Inhibitor 99.64%
    BML-280 (VU0285655-1) is a potent and selective phospholipase D2 (PLD2) inhibitor. BML-280 has the ability to prevent caspase-3 cleavage and reduction in cell viability induced by high glucose. BML-280 can be used for rheumatoid arthritis research.
    BML-280
  • HY-N8277
    Kdo2-Lipid A ammonium
    		Inducer 99.00%
    Kdo2-Lipid A ammonium is a chemically defined lipopolysaccharide (LPS) with endotoxin activity equal to LPS. Kdo2-Lipid A ammonium is highly selective for TLR4. Kdo2-Lipid A ammonium stimulates the release of both TNF and PGE2.
    Kdo2-Lipid A ammonium
  • HY-P2612
    WP9QY
    		Antagonist 99.78%
    WP9QY, TNF-a Antagonist, TNF-a Antagonist is a biological active peptide. (This cyclic peptide is designed to mimic the most critical tumor necrosis factor (TNF) recognition loop on TNF receptor I. It prevents interactions of TNF with its receptor. This TNF antagonist is a useful template for the development of small molecular inhibitors to prevent both inflammatory bone destruction and systemic bone loss in rheumatoid arthritis.)
    WP9QY
  • HY-P99663
    Inezetamab
    		Inhibitor 99.77%
    Inezetamab is a bispecific anti-CD40 and anti-MSLN IgG1 monoclonal antibody.
    Inezetamab
  • HY-138793
    2-(2,6-Dioxopiperidin-3-yl)phthalimidine
    		Inhibitor 99.67%
    2-(2,6-Dioxopiperidin-3-yl)phthalimidine (EM-12), a teratogenic Thalidomide analogue, is more active than Thalidomide and is much more stable for hydrolysis. 2-(2,6-Dioxopiperidin-3-yl)phthalimidine enhances 1,2-dimethylhydrazine-induction of rat colon adenocarcinomas.
    2-(2,6-Dioxopiperidin-3-yl)phthalimidine
  • HY-P990124
    Anti-Mouse GITR Antibody (DTA-1)
    		Agonist 98.47%
    Anti-Mouse GITR Antibody (DTA-1) is a rat-derived IgG2b, λ type agonistic antibody, targeting to mouse GITR. The recommed isotype control of Anti-Mouse GITR Antibody (DTA-1) is Rat IgG2b kappa, Isotype Control (HY-P990682).
    Anti-Mouse GITR Antibody (DTA-1)
  • HY-W026772
    Fluorene
    		Activator 99.35%
    Fluorene is an orally active polycyclic aromatic hydrocarbon (PAH) and a precursor to other fluorene-based compounds. Fluorene and its derivatives serve as dye precursors for fluorene synthesis. In A549 cells, Fluorene induces oxidative stress and inflammatory responses by increasing ROS and SOD generation, exacerbating lipid peroxidation, modulating antioxidant enzyme activity, and upregulating the expression of pro-inflammatory factors TNF-α and IL-6. In vivo, Fluorene exhibits anxiolytic activity. Fluorene holds potential for research in inflammation and neurological disorders.
    Fluorene
  • HY-P990040
    Exlinkibart
    		Inhibitor 99.66%
    Exlinkibart (LVGN-6051) targets TNFRSF9 and is an IgG1κ antibody humanized through complementarity-determining region (CDR) grafting technology.
    Exlinkibart
  • HY-P990067
    Evunzekibart
    		Inhibitor
    Evunzekibart (ATOR-1017) is an Fc-γ receptor conditional 4-1BB agonist and IgG4-type antibody. Evunzekibart can be used as monotherapy or in combination with anti-PD1 to exert anticancer activity.
    Evunzekibart
  • HY-P99605
    Cinrebafusp alfa
    		Inhibitor 98.53%
    Cinrebafusp alfa (PRS 343) is a high affinity CD137/HER2 bispecfic anticalin-based drug. Cinrebafusp alfa binds to recombinant human HER2 (Kd=0.3 nM) and human monomeric CD137 (4-1BB; Kd=5 nM). Cinrebafusp alfa facilitates T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation, further enhancing T-cell receptor-mediated activity and leading to tumor destruction. Cinrebafusp alfa has the potential for HER2+ solid tumors research.
    Cinrebafusp alfa
  • HY-P99321
    Teneliximab
    		Inhibitor ≥99.0%
    Teneliximab (BMS-224819) is a chimeric monoclonal antibody, blocks the CD40-CD40L interaction. Teneliximab (BMS-224819) has partial agonist activity resulting in some signaling through CD40 and peripheral B cell depletion.
    Teneliximab
  • HY-Y1322
    Triphenyl phosphate
    		Activator 99.67%
    Triphenyl phosphate is an organic phosphate flame retardant. Triphenyl phosphate can disrupt placental tryptophan metabolism by activating MAOA/ROS/NFκB, leading to abnormal neurological behavior. Triphenyl phosphate promotes oxidative stress by inducing inflammatory factors like nuclear factor kappa B (NFκB), interleukin-6, and tumor necrosis factor α. Triphenyl phosphate can also cause allergic contact dermatitis.
    Triphenyl phosphate
  • HY-P990134
    Anti-Mouse CD40L/CD154 Antibody (MR-1)
    		Inhibitor 99.62%
    Anti-Mouse CD40L/CD154 Antibody (MR-1) is a Armenian hamster-derived IgG type antibody inhibitor, targeting to mouse CD40L/CD154.
    Anti-Mouse CD40L/CD154 Antibody (MR-1)
  • HY-N8435
    Desoxo-narchinol A
    		Inhibitor ≥98.0%
    Desoxo-narchinol A is an orally active and potent anti-inflammatory agent. Desoxo-narchinol A can be isolated from the roots and rhizomes of Nardostachys jatamansi. Desoxo-narchinol A can be used for septic shock and inflammatory diseases research.
    Desoxo-narchinol A
  • HY-147078
    EJMC-1
    		Inhibitor 99.69%
    EJMC-1 is a moderately potent TNF-α inhibitor with an IC50 value of 42 μM.
    EJMC-1
  • HY-P2663
    Acetyl tetrapeptide-2
    		99.70%
    Acetyl tetrapeptide-2 is a bioactive peptide with anti-aging effect and has been reported used as a cosmetic ingredient.
    Acetyl tetrapeptide-2
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.