The case of the disappearing drug target.
In this issue of Molecular Cell, Hoshi et al. (2010) report two examples in which small molecule inhibitors are rendered ineffective when their kinase targets are involved in protein-protein interactions, highlighting differences between in vivo and in vitro inhibition kinetics.
Prince
John T
JT
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
Ahn
Natalie G
NG
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D051658:KCNQ2 Potassium Channel / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
D054758:A Kinase Anchor Proteins; D051658:KCNQ2 Potassium Channel; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C