title: Novel approaches for targeting kinases: allosteric inhibition, allosteric activation and pseudokinases.
abstract: 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.affiliation: Novartis Institutes for Biomedical Research, Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Cowan-Jacob
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jahnke
authors.forename: Stefan
authors.initials: S
authors.lastname: Knapp
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000495:Allosteric Site; D001665:Binding Sites; D030562:Databases, Protein; D006801:Humans; D062105:Molecular Docking Simulation; D010599:Pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases