Fragment-Based Drug Discovery Approaches
This issue of Current Topics in Medicinal Chemistry focuses on Fragment-based Drug Discovery Approaches and aims to provide readers with both an overview of major methods of the field as well as offering insights from specific case studies.
The poet Browning included “less is more” in his fabled poem to Lucrezia and this “minimalist” philosophy can readily be associated with the recent flurry of interest in fragment-based drug discovery approaches. This is exciting science! The figure below plots the number of references cited when “fragment-based” is entered as a literature search term. Interest is growing and reports of the impact of these new methods in aiding in the identification of clinical candidates against various targets have appeared. For a recent compelling review please see P.J. Hajduk and J. Greer, Nature Reviews Drug Discovery, 2007, 6(3), 211-219, A decade of fragment-based drug design: strategic advances and lessons learned.
The issue begins with a contribution by Alex et al. describing the conceptual and computational principles that serve as the theoretical basis for fragment-based approaches. With that as background, Hubbard et al. then present a clear description of a combination of experimental approaches to reducing the broad concepts to an implemented reality. Hesterkamp et al. overviews a variety of biophysical approaches and describes their use of Fluorescence Correlation Spectroscopy techniques with specific application to the discovery of inhibitors of prostaglandin D synthase. Zartler and Mo offer a discussion of the practical aspects of NMR-based fragment discovery. AstraZeneca contributes their approaches to fragment-based lead generation with selected examples. Neumann et al. describe their work with chemical microarrays of fragments and surface plasmon resonance detection methods with application to thrombin and PDE.
The interested reader should also be aware of the superb monograph edited by Erlanson and Jahnke entitled Methods and Principles in Medicinal Chemistry (2006), 34 (Fragment-Based Approaches in Drug Discovery).
It has been our pleasure to work with the contributors to this issue and with Dr. Allen Reitz and the Bentham team. Enjoy!