TH 1020
目录号 : GC50374
TH 1020是一种Toll样受体5（TLR5）/鞭毛蛋白复合物拮抗剂，IC50值为0.85μM。
Cas No.:1841460-82-9
Sample solution is provided at 25 µL, 10mM.
TH 1020 is a Toll-like receptor 5 (TLR5)/flagellin complex antagonist with an IC50 value of 0.85μM[1]. TH 1020 can inhibit flagellin-induced TLR5 signaling, but is ineffective against TLR2, TLR3, TLR4, TLR7, and TLR8[2]. TH 1020 inhibits downstream signaling by binding to the molecular interface between TLR5 dimers, disrupting the formation of functional tetramer complexes[3]. TH 1020 can inhibit TLR5 signaling in CD8+ T cells[4].
In vitro, pretreatment of IPEC-J2 cells infected with enterotoxigenic Escherichia coli (ETEC) strain C83901 with TH 1020 (1.5μM) for 2h completely inhibited the secretion of intracellular IL-17C[5]. Treatment of primary peripheral blood mononuclear cells (PBMCs) with TH 1020 (0.75, 1.5μM) significantly reduced the production of nitric oxide (NO) induced by flagellin and high mobility group protein B1 (HMGB1)[6].
In vivo, intraperitoneal injection of TH 1020 (100μg) for 4 days in ovarian cancer model mice significantly reduced the number of CCR2+ Ly6C+ cells in the tumor microenvironment and the total number of tumor-infiltrating macrophages[7].
References:
[1] Patra M C, Choi S. Recent progress in the development of Toll-like receptor (TLR) antagonists[J]. Expert opinion on therapeutic patents, 2016, 26(6): 719-730.
[2] Yan L, Liang J, Yao C, et al. Pyrimidine triazole thioether derivatives as Toll‐like receptor 5 (TLR5)/flagellin complex inhibitors[J]. ChemMedChem, 2016, 11(8): 822-826.
[3] Leifer C A, Medvedev A E. Molecular mechanisms of regulation of Toll-like receptor signaling[J]. Journal of Leucocyte Biology, 2016, 100(5): 927-941.
[4] Kang X, Liu C, Ding Y, et al. Roseburia intestinalis generated butyrate boosts anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8+ T cells[J]. Gut, 2023, 72(11): 2112-2122.
[5] Luo Y, Xu J, Zhang C, et al. Toll-like receptor 5-mediated IL-17C expression in intestinal epithelial cells enhances epithelial host defense against F4+ ETEC infection[J]. Veterinary research, 2019, 50(1): 48.
[6] Das N, Dewan V, Grace P M, et al. HMGB1 activates proinflammatory signaling via TLR5 leading to allodynia[J]. Cell reports, 2016, 17(4): 1128-1140.
[7] Kolli S H, McGinty M T, Putelo A M, et al. Ovarian Cancer Drives TLR5-Dependent Expansion of Myeloid Progenitors Through Systemic Dissemination of Ligands[J]. bioRxiv, 2025: 2025.06. 10.658497.
TH 1020是一种Toll样受体5（TLR5）/鞭毛蛋白复合物拮抗剂，IC50值为0.85μM[1]。TH 1020能够抑制鞭毛蛋白诱导的TLR5信号传导，对TLR2、TLR3、TLR4、TLR7和TLR8无效[2]。TH 1020通过结合TLR5二聚体之间的分子界面，破坏功能性四聚体复合物的形成，从而抑制下游的信号传导[3]。TH 1020能够抑制CD8+ T细胞中的TLR5信号传导[4]。
在体外，TH 1020（0.5μM）预处理产肠毒素大肠杆菌（ETEC）菌株C83901感染的IPEC-J2细胞2h，完全抑制了细胞内IL-17C的分泌[5]。TH 1020（0.75, 1.5μM）处理原代外周血单个核细胞（PBMC），显著减少了鞭毛蛋白和高迁移率族蛋白B1（HMGB1）诱导的一氧化氮（NO）的产生[6]。
在体内，TH 1020（100μg）通过腹腔注射处理卵巢癌模型小鼠4天，显著减少了肿瘤微环境中CCR2+ Ly6C+细胞，减少了肿瘤浸润巨噬细胞总数[7]。
| Cell experiment [1]: | |
Cell lines | IPEC-J2 monolayers |
Preparation Method | IPEC-J2 monolayers were first pre-cultured with 0.5μM TH 1020 (0.5μM), 0.5μM oligodeoxyribonucleotide (ODN) 2088 or the equivalent amount of their solvent DMSO and TE or PBS for 2h. Then, the monolayers were inoculated with the C83901 (Enterotoxigenic Escherichia coli (ETEC) reference strain) at MOI 100 for 1h, washed and further incubated for 23h. IL-17C cytokine production was analysed in the cell culture supernatant by ELISA. |
Reaction Conditions | 0.5μM; 2h |
Applications | TH 1020 almost completely inhibited the secretion of IL-17C in C83901-infected IPEC-J2 cells. |
References: | |
| Cas No. | 1841460-82-9 | SDF | |
| Canonical SMILES | N1(C(SC2=C3SC4=NC=CC=C4C3=NC=N2)=NN=C1C5=CC=NC=C5)CC6=CC=CC=C6 | ||
| 分子式 | C23H15N7S2 | 分子量 | 453.54 |
| 溶解度 | Chloroform: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2049 mL | 11.0244 mL | 22.0488 mL |
| 5 mM | 441 μL | 2.2049 mL | 4.4098 mL |
| 10 mM | 220.5 μL | 1.1024 mL | 2.2049 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
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