Chemical proteomics identifies unanticipated targets of clinical kinase inhibitors.
Kinases represent one of the most important target classes of current drug discovery efforts. However, because the vast majority of potential small-molecule therapeutics is directed toward the highly conserved ATP-binding cleft, kinase inhibitors often exhibit significant unintended off-target effects. A recent report describes a chemical proteomics methodology that enables the simultaneous in vivo quantification of the on- and off-binding targets of kinase inhibitors across hundreds of nucleotide-dependent enzymes.
Peters
Eric C
EC
Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. epeters@gnf.org
Gray
Nathanael S
NS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000070819:Discoidin Domain Receptor 1; D006801:Humans; D013058:Mass Spectrometry; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D011494:Protein Kinases; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases