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Open access, freely available online Synopses of Research Articles Automated Imaging Screen Reveals Promising Drug Candidates DOI: 10.1371/journal.pbio.0030165 The birth of combinatorial chemistry in components not targeted by known the early 1990s held out the promise that kinase inhibitors. scientists would soon synthesize trillions From the library of screened of compounds at a time and screen compounds, Shokat and colleagues up to a million a day, revolutionizing identifi ed a molecule (hydroxy-PP) that, the process of drug discovery. But though structurally related to a known synthesizing a vast library of compounds kinase inhibitor, induced morphological is just the fi rst step in the historically changes distinct from any known kinase painstaking process of determining inhibitor. What does hydroxy-PP target? whether a compound has the desired An enzyme, called carbonyl reductase effect on a target. In addition to an ever- 1 (CBR1), that acts on xenobiotics like growing library of candidate therapeutic anticancer drugs and is thought to compounds, advances in genome cause the heart damage associated with analysis have produced a growing list of daunorubicin chemotherapy. potential drug targets—drowning drug To better understand how compound researchers in an excess of riches. and enzyme interact, the authors In a new study, Kevan Shokat and solved the structure of hydroxy-PP and colleagues report a high-throughput CBR1 bound together. Knowing their screening method that substantially respective structures also suggests narrows the fi eld of candid