Fragment-based ligand discovery
Marcus M. Fischer, Roderick E. Hubbard · Molecular Interventions · 2009
From home building and decor to mass production, modular design is a standard feature of the modern age. The concept also promises to define drug discovery efforts in the near future, as a wide range of methodologies, from NMR to X-ray crystallography, are being adapted to high-throughput platforms. In particular, "fragment-based ligand discovery" describes the laboratory-driven evolution of drugs from libraries of chemical building blocks. "Evolution" is an apt word for the process, as a wide array of methods are used to define how compound fragments can be best fit into the binding sites of medically relevant target biomolecules. 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.