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-P1825A
    TNF-α (10-36), human TFA
    TNF-α (10-36), human (TFA) is a peptide of human TNF-α.
    TNF-α (10-36), human TFA
  • HY-113763
    TWEAK-Fn14-IN-1
    		Inhibitor 99.62%
    TWEAK-Fn14-IN-1 (Compound L524-0366) is a specific dose-dependent TWEAK-Fn14 inhibitor. TWEAK-Fn14-IN-1 binds specifically to the Fn14 surface with a KD of 7.12 μM. TWEAK-Fn14-IN-1 inhibits TWEAK induced glioma cell migration without any potential cytotoxic effects.
    TWEAK-Fn14-IN-1
  • HY-124339
    JNJ525
    		Inhibitor 99.93%
    JNJ525 (compound 1) is a TNFα inhibitor with the IC50 values of 1.2 μM and 1.1 μM against of TNFR1 and TNFR2, respectively.
    JNJ525
  • 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-P990726
    Abiprubart
    		99.00%
    Abiprubart is an anti-CD40 human IgG4 κ monoclonal antibody. Recommend Isotype Controls: Human IgG4 (S228P) kappa, Isotype Control (HY-P99003).
    Abiprubart
  • 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-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-N2255
    Crebanine
    		Inhibitor 99.83%
    Crebanine is an isoquinoline-like alkaloid that can be derived from Stephania. Crebanine is an antagonist of the α7-nAChR with an IC50 of 19.1 μM. Crebanine suppresses the proliferation, migration, and invasion of cancer cells, triggers reactive oxygen species (ROS) burst, and promotes apoptosis. Crebanine inhibits the AKT/FoxO3a, NF-κB and MAPK signaling pathways. Crebanine attenuates NOX2 hyperactivation, exhibits antioxidant properties by reducing reactive oxygen species and peroxidation in microglia cells. Crebanine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes. Crebanine has high inhibitory activity against gram-positive animal pathogenic bacteria. Crebanine ameliorates ischemia-reperfusion brain damage in middle cerebral artery occlusion and reperfusion (MCAO/R) rats. Crebanine significantly improves Scopolamine (HY-N0296)-induced cognitive deficits in ICR mice. Crebanine can be used for the study of hepatocellular carcinoma (HCC), cerebral ischemia and Alzheimer's disease.
    Crebanine
  • HY-120299
    KC01
    		Inhibitor 99.0%
    KC01 is an effective inhibitor of ABHD16A, with IC50s of 90 nM for hABHD16A and 520 nM for mABHD16A. KC01 significantly reduces lyso-PSs, and decreases lyso-PS and LPS-induced cytokine production in mouse macrophages .
    KC01
  • 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-N2252
    Licarin A
    		Inhibitor 99.83%
    Licarin A ((+)-Licarin A), a neolignan, significantly and dose-dependently reduces TNF-α production (IC50=12.6 μM) in dinitrophenyl-human serum albumin (DNP-HSA)-stimulated RBL-2H3 cells. Anti-allergic effects. Licarin A reduces TNF-α and PGD2 production, and COX-2 expression.
    Licarin A
  • 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-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-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-145726A
    ISIS 104838 sodium
    ISIS 104838 sodium 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 sodium
  • HY-N1731
    2′-Hydroxy-5′-methoxyacetophenone
    		Inhibitor 99.96%
    2'-Hydroxy-5'-methoxyacetophenone is an acetophenone derivative with acaricidal activities. 2'-Hydroxy-5'-methoxyacetophenone attenuates the inflammatory response via NF-κB signaling pathway. 2'-Hydroxy-5'-methoxyacetophenone exhibits significant inhibitory activity against α-amylase, collagenase and aldose reductase (AR) with IC50s of 0.928, 3.264 and 20.046 μM, highlighting its potential in combating diabetes. 2'-Hydroxy-5'-methoxyacetophenone exhibits anti-ovarian cancer activity.
    2′-Hydroxy-5′-methoxyacetophenone
  • 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-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-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-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
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.