Editors' ChoicePharmacology

Mapping Human Drug Targets in the Cell

See allHide authors and affiliations

Sci. Signal.  07 Oct 2014:
Vol. 7, Issue 346, pp. ec281
DOI: 10.1126/scisignal.2005994

To understand both the beneficial and the side effects of a drug, one would need to know its full binding profile to all cellular proteins. Savitski et al. take significant steps toward meeting this daunting challenge. They monitored the unfolding or “melting” of over 7000 human proteins and measured how small-molecule binding changes individual melting profiles. As a proof of principle, over 50 targets were identified for an inhibitor known to bind a broad spectrum of kinases. Two cancer drugs, vemurafib and Alectinib, are known to have a side effect of photosensitivity. The thermal profiling approach identified drug-protein interactions responsible for these side effects.

M. M. Savitski, F. B. M. Reinhard, H. Franken, T. Werner, M. F. Savitski, D. Eberhard, D. Martinez Molina, R. Jafari, R. B. Dovega, S. Klaeger, B. Kuster, P. Nordlund, M. Bantscheff, G. Drewes, Tracking cancer drugs in living cells by thermal profiling of the proteome. Science 346, 1255784 (2014). [Abstract] [Full Text]