Verdinexor (KPT-335) (KPT-335), a specific XPO1/CRM1 inhibitor, are orally bioavailable.

在常染色体显性多囊肾疾病模型中,腹腔注射Verdinexor（5 mg/kg）, 通过抑制XPO1减弱囊肿生长.每天两次口服Verdinexor（25 mg/kg）能够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,主要通过降低肺中促炎性细胞因子的表达,从而减少肺病毒滴度,因此产生抗病毒活性.

在Jurkat、OCI-Ly3、OCI-Ly10和CLBL1细胞中，Verdinexor以IC50分别为0.3 nM、2.1 nM、41.8 nM、和8.5 nM的浓度抑制细胞活性。对于原发性犬DLBCL细胞和表达XPO1及SINE的CLBL1细胞，KPT-335诱导细胞凋亡。Verdinexor对包括H1N1流行病毒、高致病性H5N1禽流感病毒以及新近出现的H7N9病毒株在内的多种流感病毒株具有强效的抑制作用。

Cell viability for lymphoid lines is determined by the MTS assay using CellTiter 96? 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 ?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.(Only for Reference)