生物活性

• 描述Verdinexor is a selective CRM1 (nuclear export protein Exportin 1/ XPO1) inhibitor with potency against canine tumor cells Jurkat (IC50=8.7nM) and primary canine DLBCL samples (IC50=13.3nM) in vitro. It is used as a selective inhibitor of nuclear export. Verdinexor exhibited effect on anti-virus replication, including influenza A virus and respiratory syncytial virus. Verdinexor had good efficacy against the influenza A and B virus strains tested at concentration of nanomolar range in MDCK cells. Pre-treatment with 1μM Verdinexor for 2h resulted in nuclear accumulation of vRNP in A549 cells infected with influenza virus A/WSN/33 at an MOI of 3 for 8 h. This block effect on vRNP export may due to the disruption of CRM1-NEP binding by Verdinexor. Daily administration of Verdinexor orally at dose of 20mg/kg for 3 days protected mice against disease pathology following a challenge with influenza virus A/California/04/09 or A/Philippines/2/82-X79, as well as reduced lung viral loads and proinflammatory cytokine expression.

• 动物研究
  剂量	Mice[3]: min = 10 mg/kg (p.o.), max = 50 mg/kg (p.o.); 5 mg/kg(i.v.)
  给药途径	p.o.
  动物药代数据	Animal Mice[3] Dogs[1] Dose 10 mg/kg 1.46 ± 0.0542 mg/kg Administration p.o. p.o. Cmax 1660 ng/ml 253 ± 88.3 ng/ml T1/2 4.88 h 3.88 ± 1.47 h AUC0→∞ 1810 ± 216 h·ng/mL F 0.435 AUClast 10300 h·ng/ml Tmax 1 h 3.83 ± 2.71 h AUC∞ 10800 h· g/ml AUC0→last 1760 ± 223 h·ng/mL