Fig. 1.

(a) With a non-covalent drug (left) the concentration must usually be kept above the minimum efficacious dose (purple line) to have an effect. The concentration and target inhibition are directly related. (b) With a covalent drug once the covalent bond has formed it is not necessary to maintain the free drug (dashed line) in the body at high concentrations as the drug is irreversibly bound to the target (solid line) until the target is degraded. In this case the drug concentration is not directly related to target inhibition. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)