SAR by NMR: putting the pieces together.
It has been nearly ten years since the introduction of SAR by NMR and the advent of fragment-based drug design. During this time, we have gained a tremendous amount of knowledge about protein druggability, the limits of chemical diversity, and crafting high-affinity ligands from low molecular weight, weakly binding leads. This review will describe the concept of fragment-based drug design, discuss why it works, and illustrate the power of the approach with two case studies on the design of potent inhibitors of matrix metalloproteinases and Bcl-2 family proteins.
Hajduk
Philip J
PJ
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA. philip.hajduk@abbott.com
D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2