Design of screening collections for successful fragment-based lead discovery

Abstract

A successful fragment-based lead discovery (FBLD) campaign largely depends on the content of the fragment collection being screened. To design a successful fragment collection, several factors must be considered, including collection size, property filters, hit follow-up considerations, and screening methods. In this chapter, we will discuss each factor and how it was applied to the design and assembly of one or more fragment collections in a major pharmaceutical company setting. We will also present examples and statistics of screening results from such collections and how subsequent collections can be improved. Lastly, we will provide a summary comparison of selected fragment collections from literature.