Targeting Protein Multiple Conformations: A Structure-Based Strategy for Kinase Drug Design

Title: Targeting Protein Multiple Conformations: A Structure-Based Strategy for Kinase Drug Design

Volume: 7 Issue: 14

Author(s): Liao Jie-Lou Jeffrey and Andrews C. Robert

Affiliation:

Keywords: Protein kinase, multiple conformations, catalytic cleft, binding pocket, DFG motif, αC helix, protein kinase inhibitor, resistant mutation

Abstract: 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.

Cite this article as:

Jeffrey Jie-Lou Liao and Robert C. Andrews, Targeting Protein Multiple Conformations: A Structure-Based Strategy for Kinase Drug Design, Current Topics in Medicinal Chemistry 2007; 7(14) . https://dx.doi.org/10.2174/156802607781696783