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-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-B0898
    Ceftiofur sodium
    		Inhibitor 98.03%
    Ceftiofur sodium is a cell wall synthesis inhibitor that targets bacterial penicillin-binding proteins (PBPs) and has anti-inflammatory effects in endotoxemia. Ceftiofur sodium exerts bactericidal effects by inhibiting the synthesis of bacterial cell wall peptidoglycan, leading to bacterial cell lysis. Ceftiofur sodium also inhibits the activation of NF-κB and MAPKs, thereby reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6.
    Ceftiofur sodium
  • 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-171034
    PQA-18
    		Inhibitor 99.62%
    PQA-18 is a unique PAK2 inhibitor (IC50: 10 nM). PQA-18 has immunosuppressing effects. PQA-18 suppresses IL2, IL4, IL6, and TNFα. PQA-18 inhibits the population of a subset of regulatory T cells and the immunoglobulin (Ig) production against T cell-dependent antigens as well as alleviates dermatitis in mice.
    PQA-18
  • HY-P99015
    Dacetuzumab
    		Inhibitor
    Dacetuzumab (SGN-40) is a humanized IgG1, anti-CD40 monoclonal antibody with anti-lymphoma activity. Dacetuzumab kills tumor cells via immune effector functions (antibody-dependent cellular cytotoxicity and phagocytosis [ADCC/ADCP]). Dacetuzumab ((SGN-40) can be used for multiple myeloma research.
    Dacetuzumab
  • HY-P99361
    Enavatuzumab
    		Inhibitor ≥99.0%
    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-145726
    ISIS 104838
    		Inhibitor
    ISIS 104838 is an antisense oligonucleotide agent that reduces the production of tumor necrosis factor (TNF-alpha), a substance that contributes to joint pain and swelling in rheumatoid arthritis.
    ISIS 104838
  • 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-N4285
    Negletein
    		Inhibitor 99.55%
    Negletein is a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells. Negletein shows promising anti-inflammatory activity via inhibition of TNF-α and IL-1β with IC50 values of 16.4 and 10.8 μM, respectively.
    Negletein
  • HY-N0358
    1,4-Dicaffeoylquinic acid
    		Inhibitor 98.44%
    1,4-Dicaffeoylquinic acid (1,4-DCQA) is a phenylpropanoid compound that can be isolated from Xanthii fructus and an inhibitor of xanthine oxidase (IC50: 7.36 μM). 1,4-Dicaffeoylquinic acid has anti-inflammatory activity and can inhibit the production of TNF-α induced by LPS (HY-D1056).
    1,4-Dicaffeoylquinic acid
  • HY-N2855
    Alphitolic acid
    		Inhibitor
    Alphitolic acid (Aophitolic acid) is an anti-inflammatory triterpene could found in quercus aliena. Alphitolic acid blocks Akt–NF-κB signaling to induce apoptosis. Alphitolic acid induces autophagy. Alphitolic acid has anti-inflammatory activity and down-regulates the NO and TNF-α production. Alphitolic acid can be used for cancer and inflammation research.
    Alphitolic acid
  • HY-112642
    9-Methoxycanthin-6-one
    		Inhibitor 99.80%
    9-Methoxycanthin-6-one, a canthin-6-one alkaloid, is present in intact plant parts and in callus tissues of different explants. 9-Methoxycanthin-6-one shows anti-tumor activity, inhibits LPS-induced TNF-α and IL-1β.
    9-Methoxycanthin-6-one
  • HY-W1000105
    Geranial
    		Inhibitor 99.51%
    Geranial ((E)-3,7-Dimethylocta-2,6-dienal) is a derivative of geraniol with anti-inflammatory activity. Geranial can inhibit the secretion of TNF-α and IL-6 in macrophages. Furthermore, Geranial also inhibits the secretion of IL-1β mediated by the NLRP-3 inflammasome.
    Geranial
  • HY-P99940
    Remtolumab
    		Inhibitor 99.24%
    Remtolumab (ABT-122) is a dual-variable domain immunoglobulin that neutralises both tumor necrosis factor α (TNFα) and IL-17A. Remtolumab shows dual inhibition of TNFα and IL-17A. Remtolumab can be used for rheumatoid arthritis (RA) research.
    Remtolumab
  • HY-P3585
    Epobis
    		Inhibitor 99.23%
    Epobis, a dendrimeric peptide, is a recombinant form of erythropoietin. Epobis is a potent erythropoietin receptor agonist. Epobis promotes neuritogenesis in primary motoneurons. Epobis decrease TNF release and crosses the blood-brain barrier. Epobis has anti-inflammatory and memory enhancing properties.
    Epobis
  • HY-P990018
    Boserolimab
    		Inhibitor 99.00%
    Boserolimab (MK-5890) is a humanized agonist monoclonal antibody that binds to CD27 to provide a costimulatory signal that enhances T-cell–mediated responses.
    Boserolimab
  • 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-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-N7012
    7,3',4'-Tri-O-methylluteolin
    		Inhibitor 99.28%
    7,3',4'-Tri-O-methylluteolin (5-Hydroxy-3',4',7-trimethoxyflavone) is a flavonoid with multiple biological activities. 7,3',4'-Tri-O-methylluteolin inhibits soybean lipoxygenase (LOX), with an IC50 value of 23.97 µg/mL. 7,3',4'-Tri-O-methylluteolin possesses anti-inflammatory effects in Lipopolysaccharides (HY-D1056) (LPS)-induced RAW 264.7 macrophages. 7,3',4'-Tri-O-methylluteolin inhibits the binding of MDM2 with p53 and induces apoptosis in MCF-7 breast cancer cells. 7,3',4'-Tri-O-methylluteolin also has antioxidant, antifungal and antitrypanosomal activitiessup>[4]sup>[5].
    7,3',4'-Tri-O-methylluteolin
  • HY-111326A
    Naphazoline nitrate
    		Inhibitor 99.12%
    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
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.