Novel approaches for targeting kinases: allosteric inhibition, allosteric activation and pseudokinases.

Journal article

Protein kinases are involved in many essential cellular processes and their deregulation can lead to a variety of diseases, including cancer. The pharmaceutical industry has invested heavily in the identification of kinase inhibitors to modulate these disease-promoting pathways, resulting in several successful drugs. However, the field is challenging as it is difficult to identify novel selective inhibitors with good pharmacokinetic/pharmacodynamic properties. In addition, resistance to kinase inhibitor treatment frequently arises. The identification of non-ATP site targeting ('allosteric') inhibitors, the identification of kinase activators and the expansion of kinase target space to include the less studied members of the family, including atypical- and pseudo-kinases, are potential avenues to overcome these challenges. In this perspective, the opportunities and challenges of following these approaches and others will be discussed.

Authors: Cowan-Jacob, S; Jahnke, W; Knapp, S

• Publication status: Published
• Publisher: Future Science
• Journal: Future medicinal chemistry
• Volume: 6
• Issue: 5
• Pages: 541-561
• Publication date: 2014-04-01
• DOI: 10.4155/fmc.13.216
• EISSN: 1756-8927
• ISSN: 1756-8919
• Language: English
• Keywords: Databases, Protein; Surface Plasmon Resonance; Allosteric Regulation; Allosteric Site; Molecular Docking Simulation; Humans; Protein Structure, Tertiary; Pharmacokinetics; Binding Sites; Protein Kinase Inhibitors; Protein Kinases