Reference systems for kinase drug discovery: chemical genetic approaches to cell-based assays.
Protein kinases play key roles in a number of diseases, including cancer, inflammation, and diabetes. Disregulation of kinase-based signal transduction networks results in aberrant cell differentiation, activation, proliferation, and invasion. The growing importance of kinases as a major class of drug targets across multiple large clinical indications, together with the large number of kinases in the genome (~518), has generated a critical need for technologies that enable the identification of potent and selective kinase inhibitors with good drug-like properties. In this review, we describe methods used for developing cell-based assays for kinase inhibitors, discuss advantages and disadvantages of each approach, and describe new chemical genetic methods as reference systems for establishing cell-based assays and their use for functional selectivity profiling of kinase inhibitors.
Whitney
J Andrew
JA
Department of Research Informatics, Cellular Genomics, Inc., Branford, CT, USA. andyw@cellulargenomics.com
D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000592:standards; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D012015:Reference Standards; D012016:Reference Values; D013678:Technology, Pharmaceutical / Q000379:methods*
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases