CU-T12-9
目录号 : GC39285
An agonist of TLR1/2
Cas No.:1821387-73-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CU-T12-9 is an agonist of the toll-like receptor 1/2 (TLR1/2) heterodimer.1 It is selective for TLR1/2 over the TLR2/6 heterodimer in a secreted alkaline phosphatase (SEAP) assay at concentrations up to 10 ?g/ml using HEK-Blue cells expressing human TLR2 and endogenously expressing both TLR1 and TLR6 and anti-TLR antibodies. CU-T12-9 (5 ?M) induces NF-κB signaling in a reporter assay. It also increases nitric oxide (NO) production in RAW 264.7 cells and primary rat macrophages at 3.6 and 0.4 ?M, respectively, and TNF-α production in RAW 264.7 cells (EC50 = 0.06 ?M).
1.Cheng, K., Gao, M., Godfroy, J.I., et al.Specific activation of the TLR1-TLR2 heterodimer by small-molecule agonistsSci. Adv.1(3)e1400139(2015)
| Cas No. | 1821387-73-8 | SDF | |
| Canonical SMILES | CNC1=CC=C(C=C1N2C=C(N=C2)C3=CC=C(C=C3)C(F)(F)F)[N+]([O-])=O | ||
| 分子式 | C17H13F3N4O2 | 分子量 | 362.31 |
| 溶解度 | DMSO: 250 mg/mL (690.02 mM) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7601 mL | 13.8003 mL | 27.6007 mL |
| 5 mM | 0.552 mL | 2.7601 mL | 5.5201 mL |
| 10 mM | 0.276 mL | 1.38 mL | 2.7601 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Specific activation of the TLR1-TLR2 heterodimer by small-molecule agonists
Sci Adv 2015;1(3):e1400139.PMID:26101787DOI:10.1126/sciadv.1400139.
Toll-like receptor (TLR) agonists activate both the innate and the adaptive immune systems. These TLR agonists have been exploited as potent vaccine adjuvants and antitumor agents. We describe the identification and characterization of a small molecule, N-methyl-4-nitro-2-(4-(4-(trifluoromethyl)phenyl)-1 H-imidazol-1-yl)aniline (CU-T12-9), that directly targets TLR1/2 to initiate downstream signaling. CU-T12-9 specifically induces TLR1/2 activation, which can be blocked by either the anti-hTLR1 or the anti-hTLR2 antibody, but not the anti-hTLR6 antibody. Using a variety of different biophysical assays, we have demonstrated the binding mode of CU-T12-9. By binding to both TLR1 and TLR2, CU-T12-9 facilitates the TLR1/2 heterodimeric complex formation, which in turn activates the downstream signaling. Fluorescence anisotropy assays revealed competitive binding to the TLR1/2 complex between CU-T12-9 and Pam3CSK4 with a half-maximal inhibitory concentration (IC50) of 54.4 nM. Finally, we showed that CU-T12-9 signals through nuclear factor κB (NF-κB) and invokes an elevation of the downstream effectors tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and inducible nitric oxide synthase (iNOS). Thus, our studies not only provide compelling new insights into the regulation of TLR1/2 signaling transduction but also may facilitate future therapeutic developments.
Luteolin restricts ASFV replication by regulating the NF-κB/STAT3/ATF6 signaling pathway
Vet Microbiol 2022 Oct;273:109527.PMID:35961273DOI:10.1016/j.vetmic.2022.109527.
African swine fever (ASF) is a devastating infectious disease that causes significant economic losses to the pig industry worldwide. Luteolin is abundant in onion leaves, carrots, broccoli, and apple skin and exerts various biological activities, including anti-cancer and anti-virus effects. Our aim was to demonstrate the mechanism of action and potent antiviral activity of luteolin against ASF virus (ASFV) in porcine alveolar macrophages. We performed cell viability, hemadsorption, indirect immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction assays to investigate the effect of luteolin on ASFV. Notably, luteolin restricted ASFV replication in a dose-dependent manner. The anti-ASFV activity of luteolin was maintained for 24-72 h. Subsequent experiments revealed that luteolin could block multiple stages of the ASFV replication cycle, including those at 6-9 h and 12-15 h after infection, instead of directly interacting with ASFV. Moreover, ASFV infection stimulated the expression of phosphorylated nuclear factor (NF)-κB, interleukin (IL)- 6, and phosphorylated signal transducer and activator of transcription 3 (STAT3). However, luteolin downregulated ASFV-induced NF-κB, IL-6, and STAT3 expression. Importantly, NF-κB agonist CU-T12-9 weakened the inhibitory effects of luteolin on NF-κB and STAT3. Moreover, CU-T12-9 partially restored the inhibitory effect of luteolin on ASFV. Similarly, luteolin reduced ASFV-induced activating transcription factor 6 (ATF6) expression, and CU-T12-9 weakened the inhibitory effect of luteolin on ATF6. Our findings suggested that luteolin inhibited ASFV replication by regulating the NF-κB/STAT3/ATF6 signaling pathway and might provide a rationale for anti-ASFV drug development.