Amenamevir

Helicase-primase:14 ng/mL

Amenamevir（ASP2151, 3-30 mg/kg/day）以剂量依赖性方式加速病毒滴度的减少，不论给药间隔如何，均可剂量依赖性降低HSV-1滴度和病损评分。根据相关性曲线，Amenamevir（口服）能完全抑制HSV-1的生长，并估算出以下药动学参数：血清中Cmax达到或超过10,000 ng/mL；AUC24h达到或超过60 μg·h/ml；T>100保持时间为21至24小时。感染后第5天，Amenamevir在血浆中的平均浓度随剂量增加而升高，3 mg Amenamevir/g或更高剂量显著降低了皮内HSV-1的滴度。

Amenamevir对HSV-1和HSV-2的平均EC50分别为14 ng/mL（范围7.7-20）和30 ng/mL（范围15-58），而Acyclovir（ACV）的相应值分别为29 ng/mL（范围18-38）和71 ng/mL（范围45-95）。

DMSO:15 mg/mL (31.08 mM)

The antiviral activities of Amenamevir and ACV against HSVs are tested using a plaque reduction assay. Briefly, HEF cells are seeded into multi-well plates and incubated until they form a monolayer. After the medium is removed, the cells are infected with HSV-1 or HSV-2, and the plates are further incubated for 1 h at 37°C. The cells are washed twice with maintenance medium and then treated with the test compound (including Amenamevir) until clear plaques appear. The cells are then fixed with 10% formalin in phosphate-buffered saline, stained with a 0.02% crystal violet solution, and the number of plaques is determined under a light microscope. The EC50, which represents the concentration of test compound needed to reduce the plaque number by 50%, is calculated using nonlinear regression analysis with a sigmoid-maximum effect (Emax) model[1].

Female hairless mice (HOS: HR-1, 7 to 8 weeks old) are infected with a suspension of HSV-1 strain WT51 (15 μL/mouse; titer, 2×108 PFU/mL) or CI-116 (15 μL/mouse; titer, 4×107 PFU/mL) in the dorsolateral skin stripped as a small square using a needle, under anesthesia. The day of HSV-1 infection is designated day zero postinfection. Total daily doses of 1, 3, 10, 30, or 100 mg/kg/day ASP2151 are orally administered to HSV-1-infected mice (n=5) for 5 days. Amenamevir (ASP2151) treatments are started 2 to 3 h after HSV infection either as a single daily dose (every 24 h, q24h) or as two (every 12 h, q12h) or three (every 8 h, q8h) divided doses. Lesion scores and intradermal HSV-1 titers are measured on day 5 postinfection[1].