Finding multiactivity substructures by mining databases of drug-like compounds.

We have developed a method, given a database of molecules and associated activities, to identify molecular substructures that are associated with many different biological activities. These may be therapeutic areas (e.g. antihypertensive) and/or mechanism-based activities (e.g. renin inhibitor). This information helps us avoid chemical classes that are likely to have unanticipated side effects and also can suggest combinatorial libraries that might have activity on a variety of receptor targets. The method was applied to the USPDI and MDDR databases. There are clearly substructures in each database that occur in many compounds and span a variety of therapeutic categories. Some of these are expected, but some are not.