Targeting protein multiple conformations: a structure-based strategy for kinase drug design.
Multiple conformations of a protein kinase target offer an opportunity to design small-molecule inhibitors with distinct but clinically useful profiles. This article analyzes and classifies the binding pockets in the kinase catalytic cleft in different conformational states. Targeting kinase multiple conformations as an emerging strategy in the field is exemplified with important small-molecule agents in the clinic. The structure-based analysis in the paper provides a rationale for thwarting the development of drug-resistant mutations in antikinase therapy.
Liao
Jeffrey Jie-Lou
JJ
TransTech Pharma Inc., 4170 Mendenhall Oaks Pkwy, High Point, NC 27265, USA. jliao@ttpharma.com
Andrews
Robert C
RC
D001665:Binding Sites; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D011487:Protein Conformation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors