TLR7-agonist-1
目录号 : GC19357
A TLR7 agonist
Cas No.:1642857-69-9
Sample solution is provided at 25 µL, 10mM.
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TLR7-agonist-1 is a potent and selective Toll-like Receptor 7 (TLR7) agonist with a LEC of 0.4 uM.
TLR7-agonist-1 is a potent and selective Toll-like Receptor 7 (TLR7) agonist with a lowest effective concentration (LEC) of 0.4 uM in HEK293 cell. TLR7-agonist-1 is found to be selective for TLR7 over TLR8 with LEC of >100 uM for human TLR8. TLR7-agonist-1 demonstrates low inhibition across five CYP450 isozymes (IC50 >10 uM) and is also not a time dependent inhibitor of CYP450 3A4. TLR7-agonist-1 has limited inhibition of the hERG potassium ion channel 3H-dofetilide binding in vitro (IC50 >50 uM)[1].
TLR7-agonist-1 is found to be rapidly cleared in conjunction with our target profile. Both Cmax and AUC increase less than dose proportionally between 0.3 and 3 mg/kg and more than dose-proportionally between 3 and 10 mg/kg. TLR7-agonist-1 can induce an antiviral interferon stimulated gene (ISG) response without inducing an IFNα response at a low dose. TLR7-agonist-1 also induces a 2.7 log decrease in serum HBV viral load from 0.3 mg/kg, and a maximum 3.1 log decrease is observed for doses between 1 and 5 mg/kg[1].
References:
[1]. McGowan DC, et al. Identification and Optimization of Pyrrolo[3,2-d]pyrimidine Toll-like Receptor 7 (TLR7) Selective Agonists for the Treatment of Hepatitis B. J Med Chem. 2017 Jul 27;60(14):6137-6151.
Cell experiment: | The ability of TLR7 agonist 2 to activate human TLR7 and/or TLR8 is assessed by using HEK293 cells. Briefly, HEK293 cells are grown in culture medium (DMEM supplemented with 10% FCS and 2 mM Glutamine). Transfected cells are then detached with Trypsin-EDTA, washed in PBS and resuspended in medium to a density of 1.67×105 cells/mL. Thirty microliters of cells are then dispensed into each well in 384-well plates, where 10 μL of TLR7-agonist-1 in 4% DMSO is already present. Following 6 hours incubation at 37°C, 5% CO2, the luciferase activity is determined by adding 15 μL of Steady Lite Plus substrate to each well and readout performed on a microplate imager. Lowest effective concentrations (LEC) values are determined for TLR7-agonist-1[1]. |
Animal experiment: | A mouse in vivo model is used to demonstrate the initial proof of concept to induce endogenous IFNα. Single oral administration of 0.3, 1, 3, and 10 mg/kg doses of TLR7 agonist 2 is given to healthy, female, fasted C57Bl/6 mice. Concentrations of TLR7 agonist 2 and mouse-IFN via ELISA are measured from the plasma and compare to vehicle[1]. |
References: [1]. McGowan DC, et al. Identification and Optimization of Pyrrolo[3,2-d]pyrimidine Toll-like Receptor 7 (TLR7) Selective Agonists for the Treatment of Hepatitis B. J Med Chem. 2017 Jul 27;60(14):6137-6151. | |
| Cas No. | 1642857-69-9 | SDF | |
| Canonical SMILES | CC1=CC(COC2=C(N(CC3=NC=CC=C3)C=C4)C4=NC(N)=N2)=NO1 | ||
| 分子式 | C17H16N6O2 | 分子量 | 336.35 |
| 溶解度 | DMSO : 160 mg/mL (475.69 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 | 2.9731 mL | 14.8655 mL | 29.7309 mL |
| 5 mM | 0.5946 mL | 2.9731 mL | 5.9462 mL |
| 10 mM | 0.2973 mL | 1.4865 mL | 2.9731 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。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet