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Recognizing and exploiting differences between RNAi and small-molecule inhibitors

The biology of RNA interference has greatly facilitated analysis of loss-of-function phenotypes, but correlating these phenotypes with small-molecule inhibition profiles is not always straightforward. We examine the rationale of comparing RNA interference to pharmacological intervention in chemical biology.

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Figure 1: Modes of action for inhibition of protein activity.

Katie Ris-Vicari

Figure 2: Alternative modes of Aurora B blockade.
Figure 3: Differential effects of siRNA and small-molecule inhibitors against p110β.

Katie Ris-Vicari

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Acknowledgements

S.S.T. is a Cancer Research UK Senior Fellow. The authors acknowledge support from the Howard Hughes Medical Institute (K.M.S.), the US National Institutes of Health (K.M.S. and W.A.W.), the Wallace H. Coulter, Pediatric Brain Tumor and Samuel G. Waxman Foundations (W.A.W.), and the Burroughs Wellcome and Thrasher Research Funds (W.A.W.).

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Weiss, W., Taylor, S. & Shokat, K. Recognizing and exploiting differences between RNAi and small-molecule inhibitors. Nat Chem Biol 3, 739–744 (2007). https://doi.org/10.1038/nchembio1207-739

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