BAY 57-1293

"目录号: HY-15303

BAY 57-1293作用于HSV helicase primase复合物，IC50为20 nM。

生物活性

Description

BAY 57-1293 represents a new class of potent inhibitors of herpes simplex virus (HSV) that target the virus helicase primase complex.IC50 Value: 20 nM (HSV-1) [1]Target: HSVin vitro: BAY 57-1293 is nearly two orders of magnitude more potent than acyclovirin vitro and the superiority was even more prominent when the viral load was increased (BAY 57-1293 IC50 = 12 nM, 20 nM and 50 nM; acyclovir IC50 = 1uM, 3M and 10?50 uM at a multiplicity of infection (m.o.i.) of 0.0025, 0.02 and 0.2, respectively). A minor increase in IC50 values at higher viral loads was observed for all thiazolyl compounds listed in Table 1. BAY 57-1293 was also active against porcine (IC50 = 5 uM) and bovine (IC50 = 0.12 uM) herpes strains [1].in vivo: Delayed treatment with BAY 57-1293 (20 mg/kg 2× daily per os, treatment day 4-14) abrogates progression of disease symptoms (mean of 10 animals per group) of HSV-2 infected guinea pigs within 1 d of treatment and healing is observed subsequently, whereas a 7.5?fold higher dose of valacyclovir (150 mg/kg 2× daily) shows marginal therapeutic efficacy compared with placebo [1]. The compound given orally, or intraperitoneally once per day at a dose of 15 mg/kg for 4 successive days was equally effective or superior to a much higher dose of famciclovir (1mg/ml, i.e. approximately 140-200mg/kg/day) given in the drinking water for 7 consecutive days, which, in our hands, is the most effective method for administering famciclovir to mice [2].Toxicity: Exploratory toxicology and safety pharmacology studies did not reveal any safety relevant findings at 30, 100 and 300 mg/kg BAY 57-1293 (once daily per os) in a 4-week chronic toxicity study in dogs. However, administration of the same dose to rats for 4 weeks resulted in a dose-dependent transitional hyperplasia of the urinary bladder epithelium [1].

Clinical Trial

NCT01658826

AiCuris Anti-infective Cures GmbH-Medpace, Inc.

Genital Herpes

October 2012

Phase 2

NCT01047540

AiCuris Anti-infective Cures GmbH-FHI 360

HSV-2

March 2010

Phase 2

NCT01658826