生物活性
GRP-60367 hydrochloride is a first-in-class potent and selective inhibitor of rabies virus (RABV) entry that specifically targets the RABV G protein. GRP-60367 inhibits entry of a subset of RABV strains. Resistance profiling of the chemotype revealed hot spots in conserved hydrophobic positions of the RABV G protein fusion loop that were confirmed in transient cell-to-cell fusion assays. Transfer of RABV G genes with signature resistance mutations into a recombinant VSV backbone resulted in the recovery of replication-competent virions with low susceptibility to the inhibitor.
化学数据
| 分子量 | 389.92 |
| 分子式 | C21H27N3O2.HCl |
| CAS号 | 1309241-34-6 (free base) |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO ≥ 100 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 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | Mouse neuronal N2a cells |
| 方法 | Virus yield reduction assays.
Mouse neuronal N2a cells (1.5 × 104 cells/well) were seeded in a 96-well plate format and incubated for 24 h. GRP-60367 was added in 3-fold serial dilutions, followed by infection of 6,000 focus-forming units (FFU) (MOI, 0.2 FFU/cell) of virus. Control wells without compound were infected in parallel with the same amount of inoculum. After 60 min, the inoculum was removed and replaced with 100 μl fresh DMEM with (treated) or without (controls) compound. Culture supernatants were collected after 48 h incubation at 34°C, and progeny virus titers were determined on N2a cells. |
| 浓度 | 100 nM, 1 uM, 10 uM, 100 uM, 1000 uM |
| 处理时间 | 48 h |
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 | 2.5646 mL | 12.8231 mL | 25.6463 mL |
| 5 mM | 0.5129 mL | 2.5646 mL | 5.1293 mL |
| 10 mM | 0.2565 mL | 1.2823 mL | 2.5646 mL |
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