| Quantitative high throughput screening (qHTS) is a new screening paradiagm in which all compounds in collection are screened with a seven-concentration titration. It provides detailed information including compound potncy and ranking order, and allows rapid clustering and SAR analysis of active compounds without cherry-picking and confirmation. We have applied this new approach to screen glucocerebrosidase inhibitors and identified three novel structure classes of the leads. Further more, their SARs were rapidly expanded based on the information from qHTS and these inhibitors showed the high selectivity over the other three hydrolases. Therefore, qHTS has been proved as an efficient method for identifying the high quality leads and facilitating the hit-to-lead progression in drug discovery. |