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Biochemistry. 2010 Dec 7;49(48):10267-76. doi: 10.1021/bi101540g. Epub 2010 Nov 12.

The chemical basis of pharmacology.

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Department of Pharmaceutical Chemistry, University of California-San Francisco, 1700 4th Street, San Francisco, CA 94158-2558, USA.


Molecular biology now dominates pharmacology so thoroughly that it is difficult to recall that only a generation ago the field was very different. To understand drug action today, we characterize the targets through which they act and new drug leads are discovered on the basis of target structure and function. Until the mid-1980s the information often flowed in reverse: investigators began with organic molecules and sought targets, relating receptors not by sequence or structure but by their ligands. Recently, investigators have returned to this chemical view of biology, bringing to it systematic and quantitative methods of relating targets by their ligands. This has allowed the discovery of new targets for established drugs, suggested the bases for their side effects, and predicted the molecular targets underlying phenotypic screens. The bases for these new methods, some of their successes and liabilities, and new opportunities for their use are described.

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