生物活性
体外研究：Verdinexor抑制Jurkat，OCI-Ly3，OCI-Ly10，和CLBL1细胞的活性，IC50分别为0.3 nM，2.1 nM，41.8 nM，和8.5 nM。KPT-335也会诱导表达XPO1与SINE 的CLBL1和原代犬DLBCL细胞凋亡。Verdinexor选择性有效抑制vRNP输出，也有效抑制各种流感病毒A和B菌株，包括流行性H1N1病毒，高致病性H5N1禽流感病毒，以及最近出现的H7N9菌株。
体内研究：Verdinexor (25 mg/kg，每天两次，p.o.)降低肺中促炎性细胞因子的表达，在体内通过减少肺病毒滴度产生抗病毒活性，并且因此降低与致死性甲型流感A病毒相关的肺疾病的发病率和死亡率。在常染色体显性多囊肾疾病模型中，Verdinexor (5 mg/kg, i.p.)通过抑制XPO1减弱囊肿生长。
化学数据
| 分子量 | 442.32 |
| 分子式 | C18H12F6N6O |
| CAS号 | 1392136-43-4 |
| 纯度 | >98% |
| 溶解性（25°C） | 88 mg/mL in DMSO |
| 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 | Jurkat , OCI-Ly3, OCI-Ly10, and CLBL1 cell lines; primary DLBCL cells |
| 方法 | Cell viability for lymphoid lines is determined by the MTS assay using CellTiter 96(R) AQueous One Solution Cell Proliferation Assay Kit. Briefly, for lymphoid cell lines, 5×104 cells (or 1×105 primary DLBCL cells) are cultured in 100 μL of complete medium in 96-well plates in the presence of SINE compounds. After 72 hours, 20 μL of MTS solution is added to each well and cells are incubated for another 4 hours before measuring absorbance at 490 nm using a Wallac Victor 1420 Multilabel Counter. The IC50 of SINE is calculated using Prism 6 software. For the non-lymphoid cell lines, 96 well plates are seeded in triplicate in 90 μL with 2500 cells/well of OSA16, 5000 cells/well of C2, and 2500 cells/well of 323610-3. Seeded plates are cultured overnight then treated the following day with 10 μL of KPT-214 in C10 media at concentrations of 0.0001, 0.01, 0.1, 1.0, and 10 μM. Plates are collected at 92 hours, centrifuged at 1300 rpm, and supernatant is removed by inverting plates on absorbent paper. Plates are then sealed and immediately placed at –80°C for a minimum of 12 hours. Plates are then thawed and CyQUANT (R)Cell Proliferation Assay is performed following the manufacturer’s protocol. Briefly, 200 μL of the diluted working CyQUANT solution is added to each well and protected from light. Fluorescence is the measured using a SpectraMax M2 microplate reader at 480 nm excitation and 520 nm emission. Results are represented as percent of control, or plotted to calculate IC50 values at 92 hours. |
| 浓度 | ~10 μM |
| 处理时间 | 72 or 92 hours |
| 动物实验 |
|---|
| 动物模型 | Mice with mouse-adapted influenza virus strain A/California/04/09 (pH1N1) or A/Philippines/2/82-X79 (H3N2). |
| 配制 | |
| 剂量 | 25 mg/kg twice daily |
| 给药处理 | p.o. |
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 | 2.2608 mL | 11.304 mL | 22.6081 mL |
| 5 mM | 0.4522 mL | 2.2608 mL | 4.5216 mL |
| 10 mM | 0.2261 mL | 1.1304 mL | 2.2608 mL |
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