Fragment-based ligand discovery

Abstract

Over the past five years, fragment-based ligand discovery has come of age. A number of compounds that evolved from fragments have entered the clinic, and the approach is increasingly accepted as an additional route to identifying new hit compounds in pharmaceutical discovery and inhibitor design. This review will summarize the current methods and ideas prevalent in the area. We will discuss the key concepts and advantages of fragment-based discovery, the approaches adopted in designing fragment libraries, the experimental methods that have been optimized for detecting fragment binding, and the strategies for evolving fragments to hit and lead compounds.