Chemical kinomics: a powerful strategy for target deconvolution.
Kinomics is an emerging and promising approach for deciphering kinomes. Chemical kinomics is a discipline of chemical genomics that is also referred to as "chemogenomics", which is derived from chemistry and biology. Chemical kinomics has become a powerful approach to decipher complicated phosphorylation-based cellular signaling networks with the aid of small molecules that modulate kinase functions. Moreover, chemical kinomics has played a pivotal role in the field of kinase drug discovery as it enables identification of new molecular targets of small molecule kinase modulators and/or exploitation of novel functions of known kinases and has also provided novel chemical entities as hit/lead compounds. In this short review, contemporary chemical kinomics technologies such as activity-based protein profiling, T7 kinasetagged phages, kinobeads, three-hybrid systems, fluorescenttagged kinase binding assays, and chemical genomic profiling are discussed along with a novel allosteric Bcr-Abl kinase inhibitor (GNF-2/GNF-5) as a successful application of chemical kinomics approaches.
Life/Health Division, Korea Institute of Science and Technology, Seoul 130-650, Korea.
Do-Hee
DH
Kim
Taebo
T
Sim
D000494:Allosteric Regulation; D019295:Computational Biology; D055808:Drug Discovery; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D019151:Peptide Library; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry; D015398:Signal Transduction
C508526:GNF-2 compound; D019151:Peptide Library; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl