Chapter 7 - Fragment-Based Drug Discovery

Abstract

Fragment based drug discovery (FBDD) has played an important role in the past decade, helping in many cases to streamline the complex process of drug discovery from target validation to new drug application. A total of eighteen drug candidates discovered by FBDD have been advanced to clinical trials so far, and Zelboraf® (vemurafenib, PLX4032) is the first FDA-approved drug discovered using fragment-based approaches. X-ray crystallography or NMR spectroscopy was used to identify thirteen of the eighteen FBDD drug candidates. FBDD evolved as a different way to start the lead generation process in drug discovery, with the idea to collect more information while doing the same amount of work overall. The past decade has seen major advances in fragment screening technologies such as X-ray crystallography, NMR spectroscopy, and SPR. All of these seek to achieve a sustainable delivery of high-quality lead candidates that can be reliably progressed into the lead development and clinical pipeline. While new technologies facilitated fragment screening, the concepts of FBDD are still being applied on complex biological targets.