An antiviral agent
GLS4 is an antiviral agent.1 It inhibits the replication of wild-type hepatitis B virus (HBV) and the drug-resistant HBV strains rtA181T, rtA181V, and rtN236T (IC50s = 146, 145, 161, and 131 nM, respectively). GSL4 (1 and 10 ?M) inhibits the formation of viral capsids and decreases viral core protein levels in HBV-infected HepG2 and HepG2.2.15 cells. It inhibits HBV replication and reduces the levels of viral intracellular core antigens in mice inoculated with HepAD38 cells, which carry and replicate HBV, when administered at doses ranging from 7.5 to 60 mg/kg.2
1.Wang, X.-Y., Wei, Z.-M., Wu, G.-Y., et al.In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutationsAntivir. Ther.17(5)793-803(2012) 2.Wu, G., Liu, B., Zhang, Y., et al.Preclinical characterization of GLS4, an inhibitor of hepatitis B virus core particle assemblyAntimicrob. Agents Chemother.57(11)5344-5354(2013)
|
Cell experiment: |
HepAD38 cells are grown to about 80% confluence in 0.3 μg/mL of tetracycline (TET). After the removal of TET, the cells are treated with different doses of Morphothiadin (GLS4), or no drug. Cell viability is monitored by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay[2]. |
|
Animal experiment: |
ICR mice are used to evaluate the pharmacokinetic (PK) properties of Morphothiadin (GLS4). Following oral administration of 10 mg/kg (of body weight) of Morphothiadin to male mice, the concentration of Morphothiadin in plasma is determined using liquid chromatography-tandem mass spectrometry (LC/MS/MS). For toxicity studies, ICR mice are given Morphothiadin by gavage over a 4-week period and then kept off drug for another 2 weeks. Groups consisting of 20 male plus 20 female mice are administered a vehicle (1% methyl-2-hydroxyethyl cellulose), 35.7, 118.9, or 356.6 mg/kg per day in a volume corresponding to 20 mL/kg. Ten mice per dose group are euthanized 2 weeks after the end of drug treatment. Body weight, food consumption, serum albumin levels, and adverse effects are determined[2]. |
|
参考文献: [1]. Zhou X, et al. Effects of ketoconazole and rifampicin on the pharmacokinetics of GLS4, a novel anti-hepatitis B virus compound, in dogs. Acta Pharmacol Sin. 2013 Nov;34(11):1420-6. |
|
动态评分
0.0