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-175813
    NPSR1 antagonist-1
    		Inhibitor
    NPSR1 antagonist-1 is a potent and peripherally restricted neuropeptide S receptor 1 (NPSR1) antagonist. NPSR1 antagonist-1 can inhibit IL-6, PTGS2, IL-20, and CXCL8 expression. NPSR1 antagonist-1 can reduce TNF-α cytokine levels. NPSR1 antagonist-1 can be used for the research of inflammation, such as peritonitis.
    NPSR1 antagonist-1
  • HY-162797
    PDE4-IN-18
    		Inhibitor
    PDE4-IN-18 (compound 1l) is a PDE4 inhibitor (IC50=1.55 μM) with anti-inflammatory activity. PDE4-IN-18 exerts anti-inflammatory effects by reducing excessive immune cell infiltration and intestinal membrane formation, as well as reducing the mRNA expression of pro-inflammatory cytokines (such as TNF-α and IL-6) in synovial tissue. PDE4-IN-18 can be used in the study of rheumatoid arthritis and psoriasis.
    PDE4-IN-18
  • HY-120152
    SLP7111228
    		Inhibitor
    SLP7111228 is a selective sphingosine kinase 1 (SphK1) inhibitor and anti-inflammatory agent. SLP7111228 selectively inhibits SphK1 and reduces the production of sphingosine-1-phosphate. SLP7111228 decreases lipopolysaccharide-induced TNFα and IL-1β levels. SLP7111228 alleviates obliterative pulmonary arteriopathy, increases cardiac index and decreases total pulmonary vascular resistance index. SLP7111228 can be used in research related to neuroinflammatory diseases and pulmonary hypertension.
    SLP7111228
  • HY-P991921
    TNX-1500
    		Inhibitor
    TNX-1500 is a crystallizable fragment-modified anti-CD154 antibody. TNX-1500 contains the hu5c8 fragment antigen-binding (Fab) domain from Ruplizumab (HY-P99315) and an IgG4 Fc region engineered to reduce FcγRIIa binding. TNX-1500 has significantly weaker binding affinity to FcγRI, FcγRIIaH, FcγRIIbF, FcγRIIIaF, and FcγRIIIaV compared to hu5c8 (Kd values: 8.7 nM, 7100 nM, 4900 nM, 8000 nM, 6000 nM respectively). TNX-1500 prolongs nonhuman primate renal allograft survival, prolongs nonhuman primate cardiac allograft survival. TNX-1500 can be used for the research of allograft rejection[1][2].
    TNX-1500
  • HY-178950
    Hck-IN-3
    		Inhibitor
    Hck-IN-3 (compound 2D) is an orally effective inhibitor targeting HCK (KD = 3.92 μM). Hck-IN-3 can inhibit the release of NO. Hck-IN-3 has an IC50 of 6.52 μM in RAW264.7 cells. Hck-IN-3 can inhibit the release of TNF-α, IL-6, and IL-1β in a concentration dependent manner. Hck-IN-3 downregulates the protein expression of NLRP3, ASC, pro-caspase-1, and pro-IL-1β in a concentration dependent manner. Hck-IN-3 can be used for research on acute non traumatic inflammatory conditions.
    Hck-IN-3
  • HY-178726
    Cot-IN-4
    		Inhibitor
    Cot-IN-4 (compound 32) is a potent cancer osaka thyroid (COT) kinase inhibitor with an IC50 of 6 nM. Cot-IN-4 inhibits the phosphorylation of ERK (IC50: 60 nM) and inhibits TNFα release (IC50: 60 nM). Cot-IN-4 also inhibits the formation of the pro-inflammatory cytokine IL-1β (IC50: 0.2 μM) in Uric acid (HY-B2130)-stimulated macrophages. Cot-IN-4 can be used for the study of inflammatory diseases.
    Cot-IN-4
  • HY-178353
    EGFR/Cytokine-IN-1
    		Inhibitor
    EGFR/Cytokine-IN-1 is an EGFR (IC50 = 0.03 μM) and Cytokine inhibitor (TNF-α, IC50 = 3.1 μM; IL-6, IC50 = 1.6 μM). EGFR/Cytokine-IN-1 shows potent anticancer activity on A549 and MCF7, respectively. EGFR/Cytokine-IN-1 significantly reduces IL-6 and TNF-α levels in A549 cells, and also shows promising ADMET profiles. EGFR/Cytokine-IN-1 can induce apoptosis in a dose-dependent manner. compound 5h can be used for the study of breast cancer and lung cancer.
    EGFR/Cytokine-IN-1
  • HY-182579
    CBS-3408
    		Inhibitor
    CBS-3408 is an orally active p38α MAPK inhibitor. CBS-3408 inhibits the release of TNFα and IL-1β. CBS-3408 reduces the disease severity of arthritis in mice. CBS-3408 inhibits TNFα release in a rat endotoxemia model. CBS-3408 can be used in studies related to endotoxemia and arthritis.
    CBS-3408
  • 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-178169
    ETI60
    		Inhibitor 99.51%
    ETI60 is an orally active, selective TLR inhibitor that targets the nucleoside-binding Site I on TLR7 (IC50 = 0.68 μM) and TLR9 (IC50 = 0.12 μM), sparing surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4 and TLR5). ETI60 potently inhibits endosomal TLR-mediated pro-inflammatory signaling with nanomolar activity in cellular, biophysical and in vivo assays. ETI60 modulates the expression of genes associated with inflammation. ETI60 effectively ameliorates symptoms in mouse models of psoriasis, and systemic lupus erythematosus (SLE). ETI60 can be used for autoimmune and inflammatory diseases research.
    ETI60
  • HY-P992444
    PR200
    		Inhibitor
    PR200 is an anti-Human TNFSF15/TL1A antibody.
    PR200
  • 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-119348
    Nitroparacetamol
    		Inhibitor
    Nitroparacetamol (NCX-701) is a nitric oxide (NO) donor-non-steroidal anti-inflammatory agent (NO-NSAID). Nitroparacetamol is formed by the ester linkage of Acetaminophen (HY-66005) and Nitrooxybutyroyl, aiming to combine the analgesic advantage of Acetaminophen with the organ-protective effect of nitric oxide, while expanding its anti-inflammatory activity. The analgesic spectrum of Nitroparacetamol is broader, and it is effective for painful pathological pain, and significantly reduces hepatotoxicity. Nitroparacetamol can reduce the expressions of IL-1β, TNF-α, COX-2, and iNOS.
    Nitroparacetamol
  • 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-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-201403
    LY2775240
    		Inhibitor
    LY2775240 is an orally active phosphodiesterase 4 (PDE4) inhibitor with potent inhibitory activity against PDE4A (IC50 = 0.09 nM), PDE4B (IC50 = 0.09 nM) and PDE4D (IC50 = 0.14 nM), and exhibits an IC50 of 2.4 nM against PDE4C. LY2775240 is a highly selective agent that reduces TNFα production upon immune activation. LY2775240 decreases TNFα production in rodent and rhesus monkey models. LY2775240 can be used in the research of psoriasis.
    LY2775240
  • 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
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.