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-P991645
    MDX-1115
    MDX-1115 is a humanized IgG1 monoclonal antibody targeting CD70. MDX-1115 can be used for synthesis of ADC BMS-936561.
    MDX-1115
  • HY-P3149A
    LEESGGGLVQPGGSMK TFA
    LEESGGGLVQPGGSMK TFA, a proteolysis peptide, is a component of Infliximab. LEESGGGLVQPGGSMK TFA can be used for quantitative analysis of Infliximab. Infliximab is a chimeric monoclonal IgG1 antibody that specifically binds to TNF-α.
    LEESGGGLVQPGGSMK TFA
  • HY-P991661
    AMG-172 Antibody
    AMG-172 Antibody is a CD70 targeting antibody. AMG-172 Antibody can be used for synthesis of ADC AMG-172.
    AMG-172 Antibody
  • HY-P991466
    Anti-CD27 Antibody (M2191)
    		Inhibitor
    Anti-CD27 Antibody (M2191) is a human monoclonal antibody (mAb) targeting TNFRSF7/CD27. Anti-CD27 Antibody (M2191) inhibits the binding of sCD70 to human CD27 ECD-Fc. Anti-CD27 Antibody (M2191) can be used in the study of anti-tumor immunity. Recommended isotype control: Human IgG1 kappa, Isotype Control (HY-P99001).
    Anti-CD27 Antibody (M2191)
  • HY-P10995
    TAT-327
    		Inhibitor
    TAT-327 is cell-penetrating peptide. TAT-327 selectively inserts into cancer cell membranes and shows potent antitumor activity. TAT-327 effectively inhibits cancer cells proliferation, induces apoptosis and disrupts EGFR signal pathway by inhibiting downstream signals (such as IL-2, TNF-α and IFN-γ) expression and the Eps8/EGFR interaction. TAT-327 significantly inhibits tumor growth in HT-29 xenograft mcie models.
    TAT-327
  • HY-172608
    TNF-α-IN-24
    		Inhibitor
    TNF-α-IN-24 (Example 15) is a TNF-α inhibitor with an IC50 of 4.1 nM. TNF-α-IN-24 can be used in study of inflammatory and autoimmune disorders such as rheumatoid arthritis and Crohn’s disease.
    TNF-α-IN-24
  • HY-101871
    Trehalose 6-behenate
    Trehalose 6-behenate is a Th1/Th17 skewing vaccine adjuvant.
    Trehalose 6-behenate
  • HY-P991682
    Emzotamig
    		Inhibitor
    Emzotamig is a monoclonal antibody inhibitor targeting tumor necrosis factor (TNF). Emzotamig is promising for research of autoimmune diseases associated with TNF overexpression, such as rheumatoid arthritis and ankylosing spondylitis.
    Emzotamig
  • HY-P990529
    Anti-TNFSF2/TNFa Antibody
    		Inhibitor
    The Anti-TNFSF2/TNFa Antibody is a CHO-expressed human antibody that targets TNFSF2/TNFa. The Anti-TNFSF2/TNFa Antibody contains huIgG1 heavy chain and huκ light chain, with a predicted molecular weight (MW) of 145 kDa. The isotype control for the Anti-TNFSF2/TNFa Antibody can refer to Human IgG1 kappa, Isotype Control (HY-P99001).
    Anti-TNFSF2/TNFa Antibody
  • HY-177304
    Anti-inflammatory agent 104
    		Inhibitor
    Anti-inflammatory agent 104 (Compound 26) is an anti-inflammatory compound. The IC50 of Anti-inflammatory agent 104 for the inhibition of TNF-α synthesis and release in the human macrophage cell line U937 is 0.024 nM. Anti-inflammatory agent 104 can reduce eosinophils in rat lungs by 63%.
    Anti-inflammatory agent 104
  • HY-N2464R
    Maltotetraose (Standard)
    Maltotetraose (Standard) is the analytical standard of Maltotetraose. This product is intended for research and analytical applications. Maltotetraose can be used as a substrate for the enzyme-coupled determination of amylase activity in biological fluids.
    Maltotetraose (Standard)
  • HY-P10797
    TAT-N24
    		Inhibitor
    TAT-N24 is a cell-permeable TAT peptide as a p55PIK signaling inhibitor. TAT-N24 is effective for corneal neovascularization (CNV) and ocular inflammation by inhibiting the HIF-1α/NF-κB signaling pathway in corneal suture (CS). TAT-N24 also inhibits corneal neovascularization.
    TAT-N24
  • HY-155821
    Anti-inflammatory agent 55
    		Inhibitor
    Anti-inflammatory agent 55 (compound 9j) is a derivative of Coixol and has anti-inflammatory activity. Anti-inflammatory agent 54 inhibits the NF-κB pathway and downregulates the expression of iNOS, TNF-α, IL-6 and IL-1β. Anti-inflammatory agent 54 inhibits LPS-induced nitric oxide (NO) production in RAW264.7 macrophages (IC50: 0.8 μM) and exerts in vivo anti-inflammatory activity in a mouse auricular edema model.
    Anti-inflammatory agent 55
  • HY-P991126
    Ciltistotug
    		Ligand
    Ciltistotug is a monoclonal antibody targeting human CD40 (TNFRSF5). Ciltistotug activates immune cells after binding to CD40, exerting immunostimulatory and antitumor activities. Ciltistotug is promising for research of cancer immunotherapy.
    Ciltistotug
  • HY-18759
    BMS-751324
    		Inhibitor
    BMS-751324 is a p38α MAPK inhibitor. BMS-751324 equips a precursor of carbamyl-methyl linkage, containing esters and phosphate functional groups derived from hydroxyphenylacetic acid (HPA). BMS-751324 effectively inhibits foot swelling and LPS-induced TNFα production in an arthritic rat model.
    BMS-751324
  • HY-P99772
    Onfekafusp alfa
    Onfekafusp alfa (L19TNF) is a homotrimer that forms from engineered peptides for the L19 antibody in scFv format fused to human TNF. Onfekafusp alfa can be used for malignant glioma research.
    Onfekafusp alfa
  • HY-114573
    TNF-α-IN-19
    		Inhibitor
    TNF-α-IN-19 is an inhibitor of TNFα that can block the interaction between TNFαRI, TRADD, and RIP1, the EC50 values for TNFα, IL-1β, and IL-1β/TNFα are 2.451, 3.792 and 1.54 μM, respectively. TNF-α-IN-19 only inhibits the degradation of IκBα when cells are stimulated by TNFα and not by IL-1β.
    TNF-α-IN-19
  • HY-176274
    FASN/SCD-IN-1
    		Inhibitor
    FASN/SCD-IN-1 is a Silybin (HY-N0779A) derivative, an orally active inhibitor of Fatty Acid Synthase (FASN)/Stearoyl-CoA Desaturase (SCD). FASN/SCD-IN-1 has shown in vitro activity in inhibiting lipid deposition, reducing FASN and SCD transcriptional levels, and exhibiting antioxidant, anti-inflammatory, and anti-fibrotic activities. FASN/SCD-IN-1 has demonstrated significant hepatoprotective effects in a rat model of acute liver injury. FASN/SCD-IN-1 ameliorates the pathological features of MASH liver, including steatosis, inflammation, and fibrosis in a mouse model of myeloproliferative steatohepatitis (MASH). FASN/SCD-IN-1 can be used to study MASH.
    FASN/SCD-IN-1
  • HY-N16450
    Cnidilide
    		Inhibitor
    Cnidilide is a natural product of alkylphthalein. Cnidilide can be isolated from the rhizomes of Cnidium officinale. Cnidilide reduces the production of NO and PGE2 by inhibiting the expression of iNOS and COX-2 induced by LPS (HY-D1056). Cnidilide can inhibit pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Cnidilide can specifically inhibit the phosphorylation of p38 MAPK and JNK, as well as the activation of downstream kinase MSK-1. Cnidilide blocks the signaling pathway by inhibiting the transcriptional activity of AP-1 and NF-κB. can be used for research on inflammation conditions.
    Cnidilide
  • HY-143410
    Anti-inflammatory agent 16
    		Inhibitor
    Anti-inflammatory agent 16 (compound 14), a peptidomimetic, shows potent anti-inflammatory activity. Anti-inflammatory agent 16 reduces TNFα, NO, CD40 and CD86 expression level.
    Anti-inflammatory agent 16
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.