1. Signaling Pathways
  2. Apoptosis
  3. TNF Receptor

TNF Receptor (肿瘤坏死因子)

Tumor Necrosis Factor Receptor; TNFR

肿瘤坏死因子 (TNF) 是细胞凋亡以及炎症和免疫的主要介质,并且与多种人类疾病的发病机制有关,包括败血症、糖尿病、癌症、骨质疏松症、多发性硬化症、类风湿性关节炎和炎症性肠病。

TNF-α 是一种 17 kDa 蛋白质,由 157 个氨基酸组成,在溶液中为同源三聚体。在人类中,该基因位于 6 号染色体上。其生物活性主要受可溶性 TNF-α 结合受体的调节。TNF-α 主要由活化的巨噬细胞、T 淋巴细胞和自然杀伤细胞产生。已知多种其他细胞的表达较低,包括成纤维细胞、平滑肌细胞和肿瘤细胞。在细胞中,TNF-α 合成为 pro-TNF (26 kDa),它与膜结合,在 TNF 转换酶 (TACE) 裂解其 pro 结构域后释放。

许多 TNF 诱导的细胞反应是由两种 TNF 受体 TNF-R1 和 TNF-R2 中的任一种介导的,这两种受体都属于 TNF 受体超家族。在 TNF 治疗后,转录因子 NF-κB 和 MAP 激酶(包括 ERK、p38 和 JNK)在大多数类型的细胞中被激活,在某些情况下,也可能诱导细胞凋亡或坏死。然而,诱导细胞凋亡或坏死主要是通过 TNFR1 实现的,TNFR1 也称为死亡受体。NF-κB 和 MAPK 的激活在多种细胞因子和免疫调节蛋白的诱导中起着重要作用,并且对许多炎症反应至关重要。

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-107352R
    Fosfenopril (Standard)

    福辛普利拉EP杂质A) (Standard)

    Inhibitor
    Fosfenopril (Standard)是 Fosfenopril 的分析标准品。本产品用于研究及分析应用。Fosfenopril (Fosinoprilat) 是一种有效的血管紧张素转换酶 (ACE) 抑制剂。Fosfenopril 通过抑制单核细胞中 TLR4/NF-κB 信号通路缓解脂多糖 (LPS) 诱导的炎症反应。
    Fosfenopril (Standard)
  • HY-P991525
    2141-V11 Agonist
    2141-V11 是一种抗 CD40 激动剂抗体,与 FcγRIIB 结合增强。2141-V11 在体内可引发有效的肿瘤特异性 T 细胞应答。2141-V11 可用于研究 BCG 无反应性非肌层浸润性膀胱癌。
    2141-V11
  • HY-P99820
    Ranevetmab
    Ranevetmab (NV-01) 是一种犬源化的抗 NGF 单克隆抗体 (mAb)。Ranevetmab 可减轻疼痛,用于退行性关节病 (DJD) 疼痛的研究。
    Ranevetmab
  • HY-P991455
    PTX-35 Agonist
    PTX-35 是一种靶向 TNFRSF25 的人类 IgG 单克隆抗体 (mAb)。PTX-35 在小鼠黑色素瘤模型中,可降低调节性 T 细胞的抑制活性并增强 CD4+ T 细胞效应反应。PTX-35 可用于胰岛细胞移植排斥和实体瘤的研究。推荐同型对照:Human IgG1 kappa,Isotype Control (HY-P99001)。
    PTX-35
  • HY-P990526
    Anti-TNFRSF21/DR6/CD358 Antibody Inhibitor
    Anti-TNFRSF21/DR6/CD358 Antibody 是 CHO 表达的人源化抗体,靶向 TNFRSF21/DR6/CD358。Anti-TNFRSF21/DR6/CD358 Antibody 带有 huIgG1 型重链和 huκ 型轻链,其预测的分子量 (MW) 为 150 kDa。Anti-TNFRSF21/DR6/CD358 Antibody 的同型对照可参考 Human IgG1 kappa, Isotype Control (HY-P99001)。
    Anti-TNFRSF21/DR6/CD358 Antibody
  • HY-173404
    VB-85247 Inducer
    VB-85247 是一种 STING 激动剂。VB-85247 通过激活 STING 通路,诱导炎症细胞因子 IFNα/β、TNFα、IL6 和 CXCL10 的上调,以及树突状细胞的成熟和活化。VB-85247 可实现膀胱内肿瘤的消退,能够用于膀胱癌的研究。
    VB-85247
  • HY-106359
    Delmitide Inhibitor
    Delmitide (RDP58) 是一种 具有有效的抗炎活性的 d-异构体十肽,具有口服活性。Delmitide 抑制 TNF-α、IFN-γ 和白细胞介素 (IL)-12 的产生,并上调血红素加氧酶 1 的活性。Delmitide 可用于溃疡性结肠炎的研究。
    Delmitide
  • HY-P991408
    DLX-105 Inhibitor
    DLX-105 是一种靶向 TNFSF2/TNFa 的人类单克隆抗体 (mAb)。DLX-105 可降低皮肤表皮厚度和K16、Ki67 表达。DLX-105 可下调IL-17、TNF-α、IL-23p19、IL-12p40 和 IFN-γmRNA 水平。DLX-105 可用于银屑病的研究。
    DLX-105
  • HY-170686
    BRD4 Inhibitor-38 Inhibitor
    BRD4 Inhibitor-38 (Compound 25) 是一种具有口服活性的 BRD4 抑制剂, 其对 BRD4 BD1BRD4 BD2IC50 值分别为 3.64 μM 和 0.12 μM。BRD4 Inhibitor-38 具有抗炎活性,其对一氧化氮 (NO) 生成的 IC50 值为 1.98 μM。
    BRD4 Inhibitor-38
  • HY-P991070
    ADG-106 Agonist
    ADG-106 是一种针对 CD137 (4-1BB) 的全人源激动剂型单克隆 IgG4 抗体。ADG-106 具有通过强 FcγRIIB 介导的交联激活 CD137 的机制,同时拮抗 CD137 配体。ADG-106 的同型对照可参考 Human IgG4 (S228P) kappa, Isotype Control (HY-P99003)。
    ADG-106
  • HY-160435
    TNF-α-IN-14 Inhibitor
    TNF-α-IN-14 是一种有效的选择性 TNFα 抑制剂,IC50 值为 1.1 µM。TNF-α-IN-14 具有抗炎特性 (WO2001072735A2; compound 12)。
    TNF-α-IN-14
  • HY-12385
    Ximoprofen Inhibitor
    Ximoprofen 是一种丙酸非甾体抗炎剂 (NSAID),具有抗炎作用。Ximoprofen可用于强直性脊柱炎的研究。
    Ximoprofen
  • HY-P991407
    PF-05230905 Inhibitor
    PF-05230905 是一种靶向 TNFSF2/TNFa 的人类单克隆抗体 (mAb)。PF-05230905 可用于类风湿关节炎的研究。
    PF-05230905
  • HY-115351
    GW-3333 Inhibitor
    GW-3333 是一种有效的口服活性 TNF-α 转换酶 (TACE) 和基质金属蛋白酶 (MMP) 抑制剂。GW-3333 抑制肿瘤坏死因子-α (TNF-α) 的产生。GW-3333 可用于关节炎研究。
    GW-3333
  • HY-168212
    PDE4-IN-22 Inhibitor
    PDE4-IN-22 (Compound 2e) 是 PDE4 抑制剂,其 IC50 值为 2.4 nM。PDE4-IN-22 具有抗炎活性,且在 Imiquimod (HY-B0180) 诱导的银屑病小鼠模型中,具有显著的抗银屑病作用。
    PDE4-IN-22
  • HY-164893
    ABBV-154 Inhibitor
    ABBV-154 是一种抗 TNF 的抗体-药物偶联物 (ADC)。ABBV-154 是由人源化抗体 Adalimumab (HY-P9908) 和糖皮质激素受体调节剂 (HY-137883) 连接组成。ABBV-154 可用于类风湿关节炎、克罗恩病和风湿性多肌痛的研究。
    ABBV-154
  • HY-N15589
    8-(6,7-Dihydroxy-3,7-dimethyl-2E-octenyloxy)psoralen Inhibitor
    8-(6,7-Dihydroxy-3,7-dimethyl-2E-octenyloxy)psoralen 是一种可以从 Citrus grandis 中发现的化合物。8-(6,7-Dihydroxy-3,7-dimethyl-2E-octenyloxy)psoralen 具有显著的抗炎活性,其主要通过抑制炎症因子 IL-1β、PGE2 和 TNF-α 的分泌发挥作用。8-(6,7-Dihydroxy-3,7-dimethyl-2E-octenyloxy)psoralen 能够用于炎症的研究。
    8-(6,7-Dihydroxy-3,7-dimethyl-2E-octenyloxy)psoralen
  • HY-P991151
    Opamtistomig Inhibitor
    Opamtistomig 是一种免疫球蛋白 (H-γ1-scFv-L-κ) 二聚体人源化单克隆抗体,靶向人程序性死亡配体 1 (PD-L1)、CD274 和肿瘤坏死因子受体超家族成员 9 (TNFRSF9)。Opamtistomig 有望用于多种实体瘤和血液肿瘤的研究。
    Opamtistomig
  • HY-N0512R
    Loganin (Standard)

    马钱子苷 (Standard)

    Inhibitor
    Loganin (Standard) 是 Loganin 的分析标准品。本产品用于研究及分析应用。Loganin 是一种环烯醚萜苷类化合物,具有抗炎、抗氧化、抗肿瘤并对急性肺损伤和肺纤维化具有保护作用。Loganin 通过上调 Nrf2/HO-1 信号通路发挥其对 LPS (HY-D1056) 介导的炎症和氧化应激的保护作用,并减少脊髓损伤 (SCI) 引起的神经炎症。
    Loganin (Standard)
  • HY-N0509R
    Astilbin (Standard)

    落新妇苷 (Standard)

    Inhibitor
    Astilbin (Standard) 是 Astilbin 的分析标准品。本产品用于研究及分析应用。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 (Standard)
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

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. 
 

Your Search Returned No Results.

Sorry. There is currently no product that acts on isoform together.

Please try each isoform separately.