| In today's drug discovery environments, cell-based assays are often applied in HTS to screen compounds with pharmacological interests. Mammalian cells with stably transfected target genes are regularly utilized, because they provide a more native host background. However, HTS with stable cells are often costly, labor intensive and time consuming. Another concern is over a prolonged time in culture, or with the shift to automated large-scale tissue culture, there is often a decrease in expression level of target genes. These could result in large variation in assay quality and compounds' pharmacological behavior. This presentation discusses the applications of a baculovirus system (BacMam) as the delivery vehicles to express drug targets, accessory proteins and reporter genes in host cells. The BacMam technology offers numerous advantages as a rapid, simple, and robust transient expression system. It enables us to complete HTS with higher quality and in shorter cycle time. The consistency of BacMam system also allows us to provide dependable SAR information for ongoing chemistry efforts. Because expression levels of target proteins can be easily adjusted, it also provides tools to study detailed pharmacology of compounds, including in condition closely mimic in vivo. Examples of applying BacMam technology in HTS and compound profiling targeting G protein-coupled receptors are presented here. |