CU-115
目录号 : GC47127
A TLR8 antagonist
Cas No.:2471982-20-2
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-115 is a toll-like receptor 8 (TLR8) antagonist (IC50 = 1.04 µM).1 It is selective for TLR8 over TLR7 (IC50 = >50 µM). CU-115 inhibits increases in type I IFN transcriptional activity induced by the ssRNA nucleic acid ligands 3p-hpRNA or G3-YSD in a luciferase reporter assay when used at concentrations of 5 and 20 µM. It decreases TNF-α and IL-1β production induced by R-848 in THP-1 cells when used at a concentration of 5 µM.
1.Padilla-Salinas, R., Anderson, R., Sakaniwa, K., et al.Discovery of novel small molecule dual inhibitors targeting toll-like receptors 7 and 8J. Med. Chem.62(22)10221-10244(2019)
| Cas No. | 2471982-20-2 | SDF | |
| Canonical SMILES | O=C(NC1=CC=C(OC2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2)C=C1)C3=C(I)C=CC=C3F | ||
| 分子式 | C21H11F7INO2 | 分子量 | 569.2 |
| 溶解度 | DMF: 10mg/mL,DMSO: 10mg/mL,DMSO:PBS (pH 7.2) (1:5): 0.15mg/mL,Ethanol: 0.25mg/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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| 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 | 1.7569 mL | 8.7843 mL | 17.5685 mL |
| 5 mM | 0.3514 mL | 1.7569 mL | 3.5137 mL |
| 10 mM | 0.1757 mL | 0.8784 mL | 1.7569 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。
Discovery of Novel Small Molecule Dual Inhibitors Targeting Toll-Like Receptors 7 and 8
J Med Chem 2019 Nov 27;62(22):10221-10244.PMID:31687820DOI:10.1021/acs.jmedchem.9b01201.
Endosomal toll-like receptors (TLRs) 7 and 8 recognize viral single-stranded RNAs, a class of imidazoquinoline compounds, 8-oxo-adenosines, 8-aminobenzodiazepines, pyrimidines, and guanosine analogues. Substantial evidence is present linking chronic inflammation mediated specifically by TLR7 to the progression of autoimmunity. We identified a new TLR7/8 dual inhibitor (1) and a TLR8-specific inhibitor (2) based on our previous screen targeting TLR8. Compound 1, bearing a benzanilide scaffold, was found to inhibit TLR7 and TLR8 at low micromolar concentrations. We envisioned making modifications on the benzanilide scaffold of 1 resulting in a class of highly specific TLR7 inhibitors. Our efforts led to the discovery of a new TLR8 inhibitor (CU-115) and identification of a TLR7/8 dual inhibitor (CU-72), bearing a distinct diphenyl ether skeleton, with potential for TLR7 selectivity optimization. Given the role of TLR8 in autoimmunity, we also optimized the potency of 2 and developed a new TLR8 inhibitor bearing a 1,3,4-oxadiazole motif.