Biochemical mechanisms of drug action: what does it take for success?


Drug discovery is extremely difficult. There are many unanticipated scientific, medical and business challenges to every drug discovery programme. It is important to increase our understanding of the fundamental properties of effective drugs so that we can anticipate potential problems in developing new agents. This article addresses potential drug discovery and development risks associated with the biochemical mechanism of drug action, and proposes simple rules to minimize these risks.

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Figure 1: Equilibrium/steady-state competitive blockade.
Figure 2: Mechanisms of non-equilibrium blockade not in mass-action equilibrium with agonist/substrate.
Figure 3: Compound progression scheme for optimizing non-equilibrium parameters.


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The author wishes to thank E. Sjogren and D. Chen for many interesting discussions.

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D.C.S. is employed by Roche Pharmaceuticals.

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Swinney, D. Biochemical mechanisms of drug action: what does it take for success?. Nat Rev Drug Discov 3, 801–808 (2004).

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