Identifying off-target effects and hidden phenotypes of drugs in human cells.

@article{MacDonald2006IdentifyingOE,
  title={Identifying off-target effects and hidden phenotypes of drugs in human cells.},
  author={Marnie L MacDonald and Jane E Lamerdin and Stephen F. Owens and Brigitte H. Keon and Graham K Bilter and Zhidi Shang and Zhengping Huang and Helen Yu and Jennifer M. Dias and Tomoe Minami and Stephen W. Michnick and John K. Westwick},
  journal={Nature chemical biology},
  year={2006},
  volume={2 6},
  pages={329-37}
}
We present a strategy for identifying off-target effects and hidden phenotypes of drugs by directly probing biochemical pathways that underlie therapeutic or toxic mechanisms in intact, living cells. High-content protein-fragment complementation assays (PCAs) were constructed with synthetic fragments of a mutant fluorescent protein ('Venus', EYFP or both), allowing us to measure spatial and temporal changes in protein complexes in response to drugs that activate or inhibit particular pathways… CONTINUE READING