生物活性
Dolutegravir (GSK1349572) is a novel potent integrase inhibitor with an IC50 of 2.7 nM in vitro. Dolutegravir (GSK1349572) is a compound for the treatment of HIV infection. Dolutegravir (GSK1349572) exhibited in vitro activity against most clinical isolates obtained from patients failing RAL-based therapy. In PBMC cell assay, Dolutegravir (GSK1349572) inhibited HIV integrase with the antiviral IC50=0.51 and IC90=2.0 nM. In MT-4 antiviral assays, potency shift extrapolated to 100% human serum was 75-fold providing PA-IC90=152 nM in PBMCs. Dolutegravir (GSK1349572) had a markedly different resistance profile as evidenced by limited cross-resistance to RAL-resistant molecular clones, by its in vitro activity against clinical isolates obtained from patients failing RAL-based therapy, and in selecting different mutations with low level FC during serial passage. In vitro experiments support the potential for Dolutegravir (GSK1349572) to have a higher genetic barrier to resistance when compared to 1st generation integrase inhibitors.
化学数据
| 分子量 | 419.38 |
| 分子式 | C20H19F2N3O5 |
| CAS号 | 1051375-16-6 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO 60 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 | MT-4 |
| 方法 | Growing MT-4 cells exponentially at a density of 500000 or 600000 /mL are infected with HIV-1 strain IIIB at a viral multiplicity of infection of 0.001 or a 50% tissue culture infective dose of 4 to 10. Then aliquoting the cells to 96-well plates in the presence of varying concentrations of S/GSK1349572. After incubation for 4 or 5 days, using the yellow tetrazolium MTT reagent [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide] to determine antiviral activity by a cell viability assay that either measured bioluminescence with a CellTiter-Glo luminescent reagent or measured absorbance at 560 and 690 nm .
|
| 浓度 | 0 to 10 μM |
| 处理时间 | 4 days or 5 days |
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 | 2.3845 mL | 11.9224 mL | 23.8447 mL |
| 5 mM | 0.4769 mL | 2.3845 mL | 4.7689 mL |
| 10 mM | 0.2384 mL | 1.1922 mL | 2.3845 mL |
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