Assessment of chemical libraries for their druggability.

Sirois, Suzanne; Hatzakis, George; Wei, Dongqing; Du, Qishi; Chou, Kuo-Chen

High throughput virtual screening is acknowledged as the initial means for identifying hit compounds that will be eventually transformed to leads or drug candidates. To improve quality of screening, it is essential to have powerful methods for the analysis of the compound databases. For this purpose, we have developed a novel and practical scoring function to assess the druggability of compounds. The proposed function consists of 12 metrics that take into account physical, chemical and structural properties as well as the presence of undesirable functional groups. We have applied this 12-metric scoring function to 44 different databases that include more than 3.8 million compounds, which are commercially available. The overall quality of each database was evaluated according to the score and rank measured by our 12-metric function. Our findings suggest that, the majority of compounds that do not satisfy druggable rules do so due to high molecular weight, high logP values and the presence of reactive functional groups.