Journal
NATURE CHEMICAL BIOLOGY
Volume 9, Issue 4, Pages 232-240Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.1199
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Funding
- US National Institutes of Health Genomics Based Drug Discovery [RL1HG004671]
- US National Institutes of Health [RL1CA133834, RL1GM084437, UL1RR024924]
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Target-identification and mechanism-of-action studies have important roles in small-molecule probe and drug discovery. Biological and technological advances have resulted in the increasing use of cell-based assays to discover new biologically active small molecules. Such studies allow small-molecule action to be tested in a more disease-relevant setting at the outset, but they require follow-up studies to determine the precise protein target or targets responsible for the observed phenotype. Target identification can be approached by direct biochemical methods, genetic interactions or computational inference. In many cases, however, combinations of approaches may be required to fully characterize on-target and off-target effects and to understand mechanisms of small-molecule action.
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