Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 25, Issue 34, Pages 7960-7980Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201805361
Keywords
drug desgin; drug discovery; inhibitors; medicinal chemistry; metalloenzymes; structure-activity relationships
Categories
Funding
- ZHAW
Ask authors/readers for more resources
Matrix metalloproteinases (MMPs) are involved in a multitude of severe diseases. Despite MMPs being considered druggable targets, past drug-discovery programs have not delivered the anticipated clinical benefits. This review examines the latest structural evolution of small-molecule inhibitors of MMPs, with a focus on the development of novel chemical entities with improved affinity and selectivity profiles. X-ray crystallographic data of the protein targets and cocrystal structures with inhibitors proved to be key for the success achieved during this ambitious endeavor. An evolutionary view on the structural diversity generated for this class of molecules is provided. This encouraging development paves the way for the clinical utilization of this class of highly relevant therapeutic targets. The structure-based design of superior MMP inhibitors highlights the power of this technique and displays strategies for the development of treatment options based on the modulation of challenging drug targets.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available