生物活性
TH5487 is a selective 8-oxoguanine DNA glycosylase 1 (OGG1) inhibitor with an IC50 of 342 nM. TH5487 (5 μM; 1 hour) decreases TNFα- and LPS-induced proinflammatory gene expression to near pretreatment levels. TH5487 stops OGG1 from recognizing its DNA substrate, inhibits DNA repair and modifies OGG1 chromatin dynamics, which results in the inhibition of proinflammatory pathway genes.
In vivo, TH5487 (prophylactic intraperitoneally injection; 8-30 mg/kg; 1-9 hours) decreases TNFα or LPS induced the robust recruitment of neutrophils to the airways, and reduces the pulmonary neutrophil count in a time-dependent manner.
化学数据
分子量 | 541.18 |
分子式 | C19H18BrIN4O2 |
CAS号 | 2304947-71-3 |
纯度 | 99.26% |
溶解性(25°C) | DMSO ≥ 13 mg/mL |
储存和运输条件 | 固体粉末: -20°C 冷藏长期储存 常温运输及临时存放 |
不同实验动物依据体表面积的等效剂量转换表(数据来源于FDA指南)
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
动物 A的Km系数 |
例如,依据体表面积折算法,将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量,需要将20 mg/kg 乘以小鼠的Km系数(3),再除以大鼠的Km系数(6),得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|
1 mM | 1.8478 mL | 9.2391 mL | 18.4781 mL |
5 mM | 0.3696 mL | 1.8478 mL | 3.6956 mL |
10 mM | 0.1848 mL | 0.9239 mL | 1.8478 mL |