Structural biology in drug design: selective protein kinase inhibitors
1Merck Research Laboratories, PO Box 2000, RY50 105, Rahway, NJ 07065, USA. giovanna_scapin@merck.com
Abstract:
Protein kinases have a fundamental role in signal transduction pathways, and aberrant kinase activity has been observed in many diseases. In recent years, kinase inhibition has become a major area for therapeutic intervention and a variety of kinase inhibitor pharmacophores has been described. This review illustrates some of the efforts and results in the field of structure-based design of protein kinase inhibitors. The methods and results discussed here illustrate the power of structure-based design in lead discovery, for example via virtual screening and in guiding the optimization of the pharmacological properties of these molecules.
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