Scaffold Mining of Publicly Available Compound Data
Ye Hu, Jürgen Bajorath · Methods and principles in medicinal chemistry · 2013
Given the rapidly increasing amounts of compound activity data that become publicly available, structure–activity relationships (SARs) can be explored on a large scale. The concept of molecular scaffolds is widely applied to aid in the rationalization of SARs. Scaffolds are derived from bioactive compounds by removal of R groups and thus represent core structures of compound series. In computational compound screening, scaffold hopping is a popular exercise. This term refers to the detection of compounds with similar activity having different core structures. In our laboratory, we are systematically analyzing scaffolds contained in compounds from medicinal chemistry resources and are studying compound–scaffold–activity relationships from different points of view. For this purpose, a variety of data mining strategies have been designed to identify scaffolds with different SAR characteristics. For example, we have detected sets of scaffolds with apparent selectivity for communities of closely related targets or promiscuity across different target families. Moreover, global scaffold hopping potential has been assessed across current pharmaceutical targets. Exemplary studies originating from our laboratory are presented herein in their scientific context.