2. Signaling Pathways
  3. Apoptosis
  4. TNF Receptor

TNF Receptor (肿瘤坏死因子)

Tumor Necrosis Factor Receptor; TNFR

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.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-N0029
    Forsythoside B

    连翘酯苷 B

    		99.99%
    Forsythoside B 是传统中药植物连翘的叶子中分离的苯乙醇苷。独一味可用于炎症疾病和促进血液循环的研究。Forsythoside B 可抑制 TNF-alpha，IL-6，IκB， 调节 NF-κB。
    Forsythoside B
  • HY-P9953
    Certolizumab pegol

    赛妥珠单抗

    		Inhibitor 99.30%
    Certolizumab pegol (Certolizumab) 是重组、聚乙二醇化、抗原结合片段的人源化单克隆抗体，可选择性靶向和中和肿瘤坏死因子-α (TNF-α)。 Certolizumab pegol 可用于类风湿关节炎和克罗恩病的研究。
    Certolizumab pegol
  • HY-110247
    TRAF-STOP inhibitor 6877002 Inhibitor 99.94%
    TRAF-STOP inhibitor 6877002，一种抑制 CD40-TRAF6 相互作用的选择性抑制剂，从专利 WO2014033122A1 中获得，抑制 RAW 细胞中 NF-κB 活化，化合物VII。TRAF-STOP 6877002 可阻止小鼠中已发生的动脉粥样硬化恶化，减少白细胞募集并减少巨噬细胞活化；减少动脉粥样硬化斑块中的巨噬细胞增殖。
    TRAF-STOP inhibitor 6877002
  • HY-N0297
    Sinensetin

    甲基化黄酮

    		Inhibitor 99.87%
    Sinensetin是一个能够在水果中发现的甲基化黄酮，有很强的抗血管和抗炎症的能力。
    Sinensetin
  • HY-N0509
    Astilbin

    落新妇苷

    		Inhibitor 99.97%
    Astilbin 是一种黄酮类化合物，可增强 NRF2 活化。Astilbin 还抑制 TNF-α 表达和 NF-κB 活化。
    Astilbin
  • HY-N0472
    Geraniin Inhibitor 99.84%
    Geraniin 是具有抗肿瘤、抗炎、抗高血糖活性的、肿瘤坏死因子α (TNF-α) 的释放抑制剂，其 IC50 值为 43 μM。
    Geraniin
  • HY-147141
    HS-276 Inhibitor 98.59%
    HS-276 是一种口服有效且高选择性的 TAK1 抑制剂，Ki 值为 2.5 nM。HS-276 对 TAK1、CLK2、GCK、ULK2、MAP4K5、IRAK1、NUAK、CSNK1G2、CAMKKβ-1 和 MLK1 具有显著抑制作用，IC50 值分别为 8.25、29、33、63、125、264、270、810、1280 和 5585 nM。HS-276 可用于类风湿关节炎 (RA) 研究。
    HS-276
  • HY-15509A
    Semapimod tetrahydrochloride Inhibitor 98.43%
    Semapimod tetrahydrochloride (CNI-1493) 是促炎细胞因子产生 (proinflammatory cytokine) 的抑制剂，可抑制TNF-α、IL-1β 和 IL-6。Semapimod tetrahydrochloride 抑制巨噬细胞 p38 MAPK 和一氧化氮生成。Semapimod tetrahydrochloride 抑制 TLR4 信号 (IC50≈0.3 μM)。Semapimod tetrahydrochloride 在多种炎症和自身免疫性疾病中具有潜在的作用。
    Semapimod tetrahydrochloride
  • HY-P9952
    Belimumab

    贝利木单抗

    		Inhibitor 99.40%
    Belimumab (LymphoStat B) 是一种人 IgG1λ 单克隆抗体，可抑制 B 细胞激活因子 (BAFF)。Belimumab 可用于系统性红斑狼疮 (SLE) 研究。
    Belimumab
  • HY-P9908A
    Adalimumab (anti-TNF-α) Inhibitor 99.62%
    Adalimumab (anti-TNF-α) 是一种人源的单克隆 IgG1 抗体，靶向肿瘤坏死因子α (TNF-α)。
    Adalimumab (anti-TNF-α)
  • HY-120323
    DRI-C21045 Inhibitor 99.02%
    DRI-C21045 (compound 10) 是一种有效和选择性的 CD40-CD40L 共刺激蛋白-蛋白质相互作用 (PPI) 抑制剂，IC50 为 0.17 μM。DRI-C21045 显示对 CD40L 诱导的 NF-κB 活化和 B 细胞增殖的浓度依赖性抑制，IC50 分别为 17.1 μM 和 4.5 μM。
    DRI-C21045
  • HY-P1860
    TNF-α (31-45), human Activator 99.77%
    TNF-α (31-45), human 是一种有效的 NF-kB 通路激活剂，也是一种促炎细胞因子，可诱导坏死或凋亡。TNF α 通过 TNFR2 刺激 NF-κB 通路，促进癌症生长、侵袭和转移。
    TNF-α (31-45), human
  • HY-N0619
    Mulberroside A

    桑皮苷 A

    		Inhibitor 99.86%
    Mulberroside A 是桑树 (Morus alba L.) 中的主要生物活性成分之一。Mulberroside A 可降低 TNF-α，IL-1β 和 IL-6 的表达，抑制 NALP3，caspase-1 和 NF-κB 的激活以及 ERK，JNK 和 p38 的磷酸化 。Mulberroside A 具有抗炎和抗细胞凋亡作用。Mulberroside A 对蘑菇酪氨酸酶 ( tyrosinase) 具有抑制活性，IC50 为 53.6 μM。
    Mulberroside A
  • HY-134471
    TNF-α-IN-2 Inhibitor 98.12%
    TNF-α-IN-2 是一种有效和具有口服活性的肿瘤坏死因子 α (TNFα) 抑制剂，在 HTRF 分析中的 IC50 值为 25 nM。结合时，TNF-α-IN-2 会使 TNFα 三聚体变形，当三聚体与 TNFR1 结合时会导致异常信号传导。TNF-α-IN-2 可用于类风湿关节炎的研究。
    TNF-α-IN-2
  • HY-147045
    UCB-5307 Inhibitor
    UCB-5307 是一种 TNF 抑制剂，对人 TNFα 的 KD 为 9 nM。UCB-5307 可以穿透预制的 hTNF/hTNFR1 复合物。
    UCB-5307
  • HY-P99056
    Utomilumab Inhibitor 99.20%
    Utomilumab (PF 05082566) 是一种人源的 IgG2 mAb 激动剂，靶向T 细胞共刺激受体 4-1BB/CD137。Utomilumab 可用于复发/难治性滤泡性淋巴瘤 (FL) 和其他 CD20+ 非霍奇金淋巴瘤 (NHL) 的研究。
    Utomilumab
  • HY-122663A
    BIO8898 Inhibitor 99.88%
    BIO8898 是一种有效的 CD40-CD154 抑制剂。BIO8898 抑制可溶性 CD40L 与 CD40-Ig 的结合，IC50 值为 25 µM。BIO8898 抑制 CD40L 诱导的细胞凋亡(apoptosis)。
    BIO8898
  • HY-N0405
    Orientin

    荭草苷

    		Inhibitor 99.02%
    Orientin 是一种神经保护剂，具有抗炎、抗氧化、抗肿瘤和心脏保护作用。Orientin 抑制 IL-6、IL-1β 和 TNF-α 的水平。Orientin 增加 IL-10 的水平。Orientin 通过抑制 TLR4 和 NF-kappa b 的信号通路发挥神经保护作用。Orientin 可用于研究神经性疼痛。
    Orientin
  • HY-N6607
    Tryptanthrin Modulator 99.89%
    Tryptanthrin 是一种吲哚喹唑啉，可以是产自靛蓝植物的生物碱。Tryptanthrin 是一种口服有效的细胞白三烯 (LT) 生物合成抑制剂。Tryptanthrin 具有抗癌活性。Tryptanthrin 可抑制 NOS1、COX-2、NF-κB 的表达水平，调节 IL-2、IL-10、TNF-α 的表达水平。
    Tryptanthrin
  • HY-111255
    SPD304 Inhibitor 99.35%
    SPD304 是肿瘤坏死因子 α (TNF-α) 的选择性抑制剂，能够促进肿瘤坏死因子三聚体的分离，从而阻断其与受体间的相互作用。SPD304 体外抑制肿瘤坏死因子 α 和受体 1 间结合的 IC50 值为 22 µM。
    SPD304
目录号 产品名 / 同用名 种属 表达系统
目录号 产品名 / 同用名 应用 反应物种
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. 
 

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z